Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study.

This corrects the article DOI: 10.1038/ejcn.2017.9.

Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study.

BACKGROUND/OBJECTIVE: Treatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (FAs) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial FA partitioning and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME trial (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy). SUBJECTS/METHODS: Sixteen participants were randomised to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15-18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or ⩾2% post intervention). RESULTS: Nine participants were stratified to DHA⩾2% (eight randomised to EPA+DHA and one to placebo) and seven to the DHA<2% group (all placebo). Compared with individuals with erythrocyte <2% change in DHA abundance, those with ⩾2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of 13C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05). CONCLUSIONS: The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment ⩾2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.

Design and rationale of the WELCOME trial: A randomised, placebo controlled study to test the efficacy of purified long chainomega-3 fatty acid treatment in non-alcoholic fatty liver disease [corrected].

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a range of liver conditions from simple fatty liver to progressive end stage liver disease requiring liver transplantation. NAFLD is common in the population and in certain sub groups (e.g. type 2 diabetes) up to 70% of patients may be affected. NAFLD is not only a cause of end stage liver disease and hepatocellular carcinoma, but is also an independent risk factor for type 2 diabetes and cardiovascular disease. Consequently, effective treatments for NAFLD are urgently needed. OBJECTIVES: The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a) liver fat percentage and b) two histologically validated algorithmically-derived biomarker scores for liver fibrosis. DESIGN: In a randomised double blind placebo controlled trial, 103 participants with NAFLD were randomised to 15-18months treatment with either 4g/day purified long chain omega-3 fatty acids (Omacor) or 4g/day olive oil as placebo. Erythrocyte percentage DHA and EPA enrichment (a validated proxy for hepatic enrichment) was determined by gas chromatography. Liver fat percentage was measured in three discrete liver zones by magnetic resonance spectroscopy (MRS). We also measured body fat distribution, physical activity and a range of cardiometabolic risk factors. METHODS: Recruitment started in January 2010 and ended in June 2011. We identified 178 potential participants, and randomised 103 participants who met the inclusion criteria. The WELCOME study was approved by the local ethics committee (REC: 08/H0502/165; www.clinicalTrials.gov registration number NCT00760513).

Clinical implications of ST-segment non-resolution after thrombolysis for myocardial infarction.

Failed reperfusion after thrombolytic therapy for acute myocardial infarction is common and signifies a poor prognosis. We investigated the clinical consequences of non-resolution of the ST segment after thrombolytic therapy for acute ST-elevation myocardial infarction, in 85 consecutive patients admitted to a coronary care unit lacking rapid access to angioplasty. Failed thrombolysis was defined as <50% ST-segment resolution 180 minutes after the start of thrombolytic treatment. Outcomes were measured in terms of in-hospital adverse events, length of hospital stay, and mortality at 6 weeks and 1 year. Thrombolysis was successful, in terms of ST-segment resolution, in 45 patients (53%). After adjustment for other factors, ST resolution was the only independent predictor of an uncomplicated recovery in hospital (odds ratio 6.8, 95% confidence interval 2.3 to 19.9; P<0.001). At 6 weeks and 1 year, overall mortality was lower in the ST resolution group, though these differences became non-significant on multivariate analysis. In patients who survived to hospital discharge, median length of stay was greater in successfully thrombolysed patients (9 days versus 8 days) despite their lower rate of complications. ST-segment resolution is a useful marker of successful thrombolysis and relates to clinical outcome. If assessed routinely it might assist, along with other clinical markers, in the identification of low-risk patients who can be discharged early.

Experimental determination of stress distributions in articular cartilage before and after sustained loading.

OBJECTIVE: To test the hypotheses that stress concentrations exist within articular cartilage, and are intensified by sustained 'creep' loading. DESIGN: Matched-pair comparison of stress distributions in cartilage, in vitro, before and after creep. BACKGROUND: The ability of cartilage to equalize contact stresses between articulating surfaces may be compromised by undulations in the subchondral bone, and by variations in chemical composition. Furthermore, any stress concentrations within cartilage may be affected by creep loading, which-reduces its water content. METHODS: Sixteen specimens of apparently normal cartilage-on-bone, 12 mm x 15 mm, were removed from the femoral condyles and tibial plateaux of patients undergoing total knee replacement. The cartilage was subjected to a nominal compressive stress of 2 MPa by means of a 10 mm-diameter flat impermeable indentor. During the 20 s loading period, a miniature pressure transducer, side-mounted in a 0.9 mm-diameter needle, was pulled through the cartilage in a direction parallel to the surface, while transducer output and position were sampled at 25 Hz. 'Stress profiles' were obtained with the transducer pointing in the 12 o'clock and 3 o'clock directions, and were repeated after creep loading at 1.6 MPa for 2 h. RESULTS: Validation tests indicated that transducer output was proportional to the average compressive stress, but overestimated it by 9-15%. Stresses were greatest under the centre of the indentor, and showed local variations ('concentrations') which were increased in number and size after creep loading. CONCLUSIONS: Measured values of compressive stress incorporate small systematic errors. Nevertheless, the results presented clearly support both hypotheses.

Monocanalicular intubation with Monoka tubes for the treatment of congenital nasolacrimal duct obstruction.

OBJECTIVE: Nasolacrimal duct intubation with Silastic tubes often is used for the treatment of congenital nasolacrimal duct obstruction. The more established intubation technique uses tubing designed for bicanalicular intubation. A commercial product now is available for monocanalicular intubation (Monoka tube, FCI, Issy-Les-Moulineaux Cedex, France), made possible by a punctal anchor attached to the proximal end of the tubing. The authors evaluated the complications and results of their experience with Silastic tube monocanalicular intubation for treatment of congenital nasolacrimal duct obstruction. DESIGN: The study design was a retrospectively reviewed clinical trial with the results compared to a historic cohort treated with an alternative medical device. PARTICIPANTS: Thirty-nine pediatric patients with 48 obstructed congenital nasolacrimal ducts were available for treatment and postoperative follow-up. The historic cohort included 25 cases of congenital nasolacrimal duct obstruction. INTERVENTION: The participants were treated with monocanalicular Silastic tube intubation. The historic cohort was treated with bicanalicular Silastic tube intubation. The tubes were left in place for 4 to 6 months before planned removal. MAIN OUTCOME MEASURES: Dye disappearance tests were performed before and after surgery after removal of the tube. Intraoperative and postoperative complications were noted. RESULTS: Significant complications of the monocanalicular tubing included 1 case of bilateral preseptal cellulitis, 1 case of migration of the punctal anchor into the canaliculus that required surgical correction, 2 cases of a corneal abrasion, 1 case of a corneal ulcer, and 21 cases of premature removal of the tube. Of the 21 cases with premature tube removal, 13 (62%) of the eyes showed an improvement in the symptoms and results of dye disappearance test. Of the 27 cases that completed the full course of tube placement, all the tubes were removed successfully in an office setting, and 25 (93%) showed an improvement in the symptoms and results of dye disappearance test. Significant complications of the authors' bicanalicular intubation include stretching of the punctum, tube dislodgement, and tube removal requiring general anesthesia to the patient. Of the authors' 25 cases treated with bicanalicular intubation, 17 (68%) showed an improvement in the symptoms and results of dye disappearance test. CONCLUSION: The recently introduced Silastic monocanalicular tubing offers an alternative to bicanalicular tubing for treatment with intubation of congenital nasolacrimal duct obstruction. Complications due to intubation persist with the monocanalicular tube. However, some of the complications the authors encountered may be avoided by a recent change in the design of the tubing and by familiarity with recommended techniques. The overall success rate of 79% with the Monoka tube is lower than that for published reports of bicanalicular intubation.

Adriamycin induces apoptosis in rat thymocytes.

Apoptosis is a controlled form of cell death accompanied by distinct morphological and biochemical changes. In this study the nature of cytotoxicity induced by adriamycin (ADM) in rat thymocytes was evaluated. Morphological and biochemical changes characteristic of apoptosis were found to precede adriamycin-induced cell death. Our findings demonstrate the involvement of c-Myc, c-Jun, antioxidant enzymes CuZn superoxide dismutase and catalase, and perhaps poly ADP ribosylation in ADM-induced cell death.

Coccidioidomycosis of the uterus.

We have described a case of coccidioidomycosis of the endometrium in a postpartum woman, living in a nonendemic area, who presented with vaginal bleeding. Diagnosis was made by demonstration of spherules in the endometrial biopsy and culture of the tissue. Eight cases of coccidioidomycosis involving the female genital tract have been reported so far. Of these, three patients died of dissemination.