Effect of DA-9701 on Gastric Emptying in a Mouse Model: Assessment by (13)C-Octanoic Acid Breath Test.

Effect of DA-9701 on gastric emptying in a mouse model: Assessment by (13)C-octanoic acid breath test.

World J Gastroenterol. 2013 Jul 21; 19(27): 4380-5
Lim CH, Choi MG, Park H, Baeg MK, Park JM

To evaluate the effects of DA-9701 on the gastric emptying of a solid meal using the (13)C-octanoic acid breath test in a mouse model.Male C57BL/6 mice aged > 8 wk and with body weights of 20-25 g were used in this study. The solid test meal consisted of 200 mg of egg yolk labeled with 1.5 L/g (13)C-octanoic acid. The mice were placed in a 130 mL chamber flushed with air at a flow speed of 200 mL/min. Breath samples were collected for 6 h. The half-emptying time and lag phase were calculated using a modified power exponential model. To assess the reproducibility of the (13)C-octanoic acid breath test, the breath test was performed two times at intervals of one week in ten mice without drug treatment. To assess the gastrokinetic effects of DA-9701, the breath test was performed three times in another twelve mice, with a randomized crossover sequence of three drug treatments: DA-9701 3 mg/kg, erythromycin 6 mg/kg, or saline. Each breath test was performed at an interval of one week.Repeatedly measured half gastric emptying time of ten mice without drug treatment showed 0.856 of the intraclass correlation coefficient for the half gastric emptying time (P = 0.004). The mean cumulative excretion curve for the (13)C-octanoic acid breath test showed accelerated gastric emptying after DA-9701 treatment compared with the saline control (P = 0.028). The median half gastric emptying time after the DA-9701 treatment was significantly shorter than after the saline treatment [122.4 min (109.0-137.9 min) vs 134.5 min (128.4-167.0 min), respectively; P = 0.028] and similar to that after the erythromycin treatment [123.3 min (112.9-138.2 min)]. The lag phase, which was defined as the period taken to empty 15% of a meal, was significantly shorter after the DA-9701 treatment than after the saline treatment [48.1 min (44.6-57.1 min) vs 52.6 min (49.45-57.4 min), respectively; P = 0.049].The novel prokinetic agent DA-9701 accelerated gastric emptying, assessed with repeated measurements in the same mouse using the (13)C-octanoic acid breath test. Our findings suggest that DA-9701 has therapeutic potential for the treatment of functional dyspepsia. HubMed – drug

Low rates of adherence for tumor necrosis factor-? inhibitors in Crohn’s disease and rheumatoid arthritis: Results of a systematic review.

World J Gastroenterol. 2013 Jul 21; 19(27): 4344-50
Fidder HH, Singendonk MM, van der Have M, Oldenburg B, van Oijen MG

To investigate adherence rates in tumor necrosis factor-? (TNF-?)-inhibitors in Crohn’s disease (CD) and rheumatoid arthritis (RA) by systematic review of medical literature.A structured search of PubMed between 2001 and 2011 was conducted to identify publications that assessed treatment with TNF-? inhibitors providing data about adherence in CD and RA. Therapeutic agents of interest where adalimumab, infliximab and etanercept, since these are most commonly used for both diseases. Studies assessing only drug survival or continuation rates were excluded. Data describing adherence with TNF-? inhibitors were extracted for each selected study. Given the large variation between definitions of measurement of adherence, the definitions as used by the authors where used in our calculations. Data were tabulated and also presented descriptively. Sample size-weighted pooled proportions of patients adherent to therapy and their 95%CI were calculated. To compare adherence between infliximab, adalimumab and etanercept, the adherence rates where graphed alongside two axes. Possible determinants of adherence were extracted from the selected studies and tabulated using the presented OR.Three studies on CD and three on RA were identified, involving a total of 8147 patients (953 CD and 7194 RA). We identified considerable variation in the definitions and methodologies of measuring adherence between studies. The calculated overall sample size-weighted pooled proportion for adherence to TNF-? inhibitors in CD was 70% (95%CI: 67%-73%) and 59% in RA (95%CI: 58%-60%). In CD the adherence rate for infliximab (72%) was highercompared to adalimumab (55%), with a relative risk of 1.61 (95%CI: 1.27-2.03), whereas in RA adherence for adalimumab (67%) was higher compared to both infliximab (48%) and etanercept (59%), with a relative risk of 1.41 (95%CI: 1.3-1.52) and 1.13 (95%CI: 1.10-1.18) respectively. In comparative studies in RA adherence to infliximab was better than etanercept and etanercept did better than adalimumab. In three studies, the most consistent factor associated with lower adherence was female gender. Results for age, immunomodulator use and prior TNF-? inhibitors use were conflicting.One-third of both CD and RA patients treated with TNF-? inhibitors are non-adherent. Female gender was consistently identified as a negative determinant of adherence. HubMed – drug

High Resolution Melting Curve Analysis for Rapid Detection of Rifampin Resistance in Mycobacterium tuberculosis: A Meta-Analysis.

J Clin Microbiol. 2013 Jul 24;
Yin X, Zheng L, Liu Q, Lin L, Hu X, Hu Y, Wang Q

Rapid, simple, accurate and affordable method for the detection of drug-resistant tuberculosis is very critical for the selection of antimicrobial therapy and patient management. High resolution melting curve analysis has been used for rifampin resistance detection of Mycobacterium tuberculosis and has shown promise. We did a systematic review and meta-analysis of published studies to evaluate the accuracy of high resolution melting curve analysis for the detection of rifampin resistance in clinical Mycobacterium tuberculosis isolates. We searched Pubmed, BIOSIS Previews and Web of Science to identify studies and included studies following predetermined criteria. We used the DerSimonian-Laird random effects model to calculated pooled measures and applied Moses’ constant of linear model to fit the Summary Receiver Operating Characteristic curve. Most of identified citations were excluded and only seven studies were included in the final analysis according to the selection criteria. The overall sensitivity of high resolution melting curve analysis was 94% (92%-96%) and the overall specificity was very high at 99% (98%-100%). Pooled positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 63.39 (30.21-133.00), 0.06 (0.04-0.09) and 892.70 (385.50-2067.24), respectively. There was no significant heterogeneity across all included studies for above mentioned measures. The Summary Receiver Operating Characteristic curve for the same data shows an area of 0.99 and a Q* of 0.97. High resolution melting curve analysis has high sensitivity and specificity for the detection of rifampin resistance in clinical Mycobacterium tuberculosis isolates. This method could be a good alternative to conventional drug susceptibility tests in clinical practice. HubMed – drug