Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications

AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal(GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors(PPIs),histamine 2-receptor antagonists(H2RA) and mucoprotective drugs(MPs) were analyzed.A defined daily dose(DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs(NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs(misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs(n = 1039) accounted for only 3.46% of total aspirin prescriptions(n = 30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs(2.82% vs 0.40%,P < 0.05) and aspirin/H2RA(2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets.The ratio of MP plus aspirin prescriptions to the total MP prescriptions was as follows:rebamipide(0.47%),teprenone(0.91%),L-glutamine and sodium gualenate granules(0.92%),gefarnate(0.31%),hydrotalcite(1.00%) and sucralfate oral suspension(0.13%).Percentages of prescriptions containing aspirin and intestinal protective drugs among the total aspirin prescriptions were:rebamipide(0.010%),PPI/rebamipide(0.027%),teprenone(0.11%),PPI/teprenone(0.037%),gefarnate(0.017%),and PPI/gefarnate(0.013%).No prescriptions were found containing coadministration of aspirin and other NSAIDs.Among the 3196 prescriptions containing aspirin/clopidogrel,3088(96.6%) prescriptions did not contain any GI protective medicines.Of the 389 prescriptions containing aspirin/corticosteroids,236(60.7%) contained no GI protective medicines.None of the prescriptions using aspirin/warfarin(n = 22) contained GI protective medicines.Thirty-five patients were admitted to this hospital in 2011 because of acute hemorrhage of upper digestive tract induced by low-dose aspirin.The annual incidence rates of major GI bleeding were estimated at 0.25% for outpatients taking aspirin and 0.5% for outpatients taking aspirin/warfarin,respectively.CONCLUSION:The prescribing pattern of low-dose aspirin revealed a poor awareness of preventing GI injury with combined protective medications.Actions should be taken to address this issue.

Drug utilization of clarithromycin for gastrointestinal disease treatment

AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use. METHODS: Using a structured pro forma,we conducted a two-month survey of the electronic prescriptions containing immediate-release (IR) or sustained-release (SR) product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS: One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori (H pylori) therapy,triple therapy take the dominant position (91.8%),followed by quadruple therapy (4.3%) and dual therapy (3.9%). Amoxicillin was the most frequently co-prescribed antibiotic.Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR,and 6.4% of prescriptions of clarithromycin IR,were prescribed at inappropriate dosing intervals. Surprisingly,disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating H pylori infection although off-label use for this purpose was reported in literature. On the contrary,only one prescription (0.9%) of clarithromycin IR was prescribed for unapproved indication (i.e. gastro-oesophageal reflux disease). 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION: There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease,especially with regard to administration schedule,concordance between indications and diagnoses and management of drug interactions.

Phosphorylation of Serine 186 of bHLH Transcription Factor SPEECHLESS Promotes Stomatal Development in Arabidopsis

The initiation of stomatal lineage and subsequent asymmetric divisions in Arabidopsis require the activity of the basic helix-loop-helix transcription factor SPEECHLESS （SPCH）. It has been shown that SPCH controls entry into the stomatal lineage as a substrate either of the MITOGEN-ACTIVATED PROTEIN KINASE （MAPK） cascade or GSK3-1ike kinase BRASSlNOSTEROID INSENSITIVE 2 （BIN2）. Here we show that three serine residues of SPCH appear to be the primary phosphorylation targets of Cyclin-Dependent Kinases A;1 （CDKA;1） in vitro, and among them Serine 186 plays a crucial role in stomatal formation. Expression of an SPCH construct harboring a mutation that results in phosphorylation deficiencies on Serine 186 residue failed to rescue stomatal defects in spch null mutants. Expression of a phosphorylation-mimic mutant SPCHS186D complemented stomatal production defects in the transgenic lines harboring the targeted expression of dominant-negative CDKA;1.N146. Therefore, in addition to MAPK- and BIN2-mediated phos- phorylation on SPCH, phosphorylation at Serine 186 is positively required for SPCH function in regulating stomatal development.

Cortical Inflammation is Increased in a DSS-Induced Colitis Mouse Model

While inflammatory bowel disease(IBD) might be a risk factor in the development of brain dysfunctions,the underlying mechanisms are largely unknown. Here,mice were treated with 5% dextran sodium sulfate(DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-a levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSSinduced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis.These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here,we provide new information on the impact of colitis on the outcomes of cortical inflammation.

A novel route to enhance high-temperature mechanical property and thermal shock resistance of low-carbon Mgo-C bricks by introducing ZrSiO_(4)

Conventional MgO-C bricks(graphite content>14 wt.%)produce a great deal of greenhouse gas emission,while low-carbon MgO-C bricks have serious thermal shock resistance during high-temperature service.To enhance the high-temperature mechanical property and thermal shock resistance of low-carbon MgO-C bricks,a novel route of introducing ZrSiO_(4) powder into low-carbon MgO-C bricks was reported in such refractories with 2 wt.% flaky graphite.The results indicate that the low-carbon MgO-C brick with 0.5 wt.%ZrSiO_(4) addition has the maximum hot modulus of rupture at 1400℃ and the corresponding specimen fired in the carbon embedded atmosphere has the maximum residual strength ratio(98.6%)after three thermal shock cycles.It is found that some needle-like AlON and plate-like Al_(2)O_(3)-ZrO_(2) composites were in situ formed in the matrices after the low-carbon MgO-C bricks were coked at 1400℃,which can enhance the high-temperature mechanical property and thermal shock resistance due to the effect of fiber toughening and particle toughening.Moreover,CO_(2) emission of the newly developed low-carbon MgO-C bricks is reduced by 58.3% per ton steel after using them as the working lining of a 90 t vacuum oxygen decarburization ladle.