The prevalence of H. pylori resistance to clarithromycin, metronidazole, levofloxacin and multiple antibiotics in coastal southeast China is high. Choice of therapy should be individualized based on a susceptibility test in this region of the country.

We confirmed that NUDT15 c.415C>T, c.36_37insGGAGTC, and c.52G>A variants were risk factors for thiopurine-induced leukopenia. Combined detection of the 3 variants could increase the predictive sensitivity of thiopurine-induced leukopenia and help to distinguish early leukopenia in heterozygote of c.415C>T in Chinese patients with IBD. Treatment monitoring by NUDT15 variants may be promising in individualized therapy.

We tested the hypothesis that a prostanoid-mediated mechanism of vascular contraction is expressed in rats with aortic coarctation-induced hypertension. Rings of descending thoracic aorta taken from normotensive and hypertensive rats were contrasted in terms of constrictor responsiveness to arachidonic acid (AA), AA-induced release of eicosanoids, and ability to convert exogenous prostaglandin (PG) H2 to PGI2. AA (10`8 to 10`mol/L) increased isometric tension in aortic rings (bathed in Krebs' bicarbonate buffer) of hypertensive but not normotensive rats. AA (10-5 mol/L) also elicited the release of PGI2, PGE2, thromboxane (TX) A2, and monohydroxyeicosatetraenoic acids (HETEs); this release from the aortic rings of hypertensive rats exceeded the corresponding release from the aortic rings of normotensive rats. However, the rate of conversion of exogenous PGH2 to PGI2 by aortic rings of hypertensive rats was <50% the rate of conversion by aortic rings of normotensive rats. The constrictor effect of AA in aortic rings of hypertensive rats was abolished by an hromboxane (TX) A2 and prostaglandin (PG) H2 stimulate contraction of vascular smooth muscle via interaction with a common receptor.1 Treatment with a blocker of TXA2-PGH2 receptors lowers the blood pressure of rats with established angiotensin II-and salt-induced hypertension2 and of rats in the early stage of the hypertension produced by complete ligation of the aorta between the renal arteries,3 a model of angiotensin-dependent hypertension. A blocker of TXA2-PGH2 receptors also was found to attenuate the constrictor effect of angiotensin II and calcium ionophore A23187 in rings of thoracic aorta taken from rats with aortic coarctation-induced hypertension but not from normotensive rats.45 From these findings, it was inferred that a pressor mechanism linked to the activation of TXA2-PGH2 receptors contributes to the increase in blood pressure and vascular contractility in angiotensin-dependent models of hypertension.2 5The present study was designed to investigate whether a prostanoid-mediated mechanism of vascular contraction is hyperexpressed in rats with aortic coarctation-induced hypertension. To inhibitor of cyclooxygenase (indomethacin, 10 gmol/L) and a blocker of TXA2-PGH2 receptors (SQ29548, 1 ,umol/L) but was not affected by an inhibitor of TXA2 synthesis (CGS13080, 10 ,umol/L), suggesting mediation by PGH2. The lipoxygenase inhibitor baicalein (75 ,umol/L) also attenuated the constrictor effect of AA in aortic rings of hypertensive rats while decreasing the associated release of HETEs and correcting the impairment in the conversion of PGH2 to PGI2. We conclude that the expression of AA-induced PGH2-mediated constriction of aortic rings is increased in hypertensive rats because of increased PGH2 formation associated with disruption in the coupling of PGH2 synthesis to PGH2 metabolism caused by a product(s) of lipoxygenase with the ability to inhibit prostacyclin synthase. (Circ Res. 1994;74:197-205.) Key Words * thromboxane-prostaglandi...

To test the hypothesis that prostanoids contribute to angiotensin H-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 fiM) to inhibit cyclooxygenase, CGS13080 (10 fiM) to inhibit thromboxane A 2 synthesis, or SQ29548 (1 fiM) to block thromboxane A^prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from nonnotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B 2 , which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10~6 M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10~6 to 10~5M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10"' M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10~6 M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoidmediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension. (Hypertension 1991;18:158-164) A ngiotensin II stimulates synthesis of prostaglandin I 2 (PGI 2 ) and E? (PG^), and these vasodilatory prostanoids, in turn, interfere with the expression of angiotensin II-induced vasoconstriction.1 It is well established that this type of angiotensin II-prostanoid interaction contributes prominently to homeostatic mechanisms that defend against the vasoconstrictor and pressor actions of angiotensin II in settings featuring increased activity of the renin-angiotensin system. 1 Several recent studies have suggested a second type of angiotensin II-prostanoid interaction, one that links vasoconstrictor prostanoids such as thromboxane A 2 (TxA 2 ) or the prostaglandin endoperoxides to the mechanisms of angiotensin II-dependent hypertension. For example, the increase of blood pressure produced by chronic infusion of angiotensin II in saline-drinking rats was attenuated by concom- itant treatment with a blocker of the receptors shared by TxA 2 and the prostaglandin endoperoxides, 2 just as the pressor response to short-term infusion of angiotensin II was attenuated by pretreatment with either a blocker of TxA^prostaglandin endoperoxide receptors or an inhibitor of thromboxane synthase. Moreover, treatment with a blocker of TxAVprostaglandin endoperoxide receptors was reported to lower t...

Introduction: Thiopurine S-methyltransferase (TPTM) is a well known biomarker for thiopurine-induced leucopenia, which has limited value in Asia. Instead, NUDT15C415T is a promising predictor in Asia. Aims:To explore whether an optimised strategy based on NUDT15 C415T genotypes affects thiopurine-induced leucopenia, as well as efficacy in Chinese patients with Crohn's disease. Methods:Patients with Crohn's disease and indications for thiopurines were included from two hospitals in China. They were randomly assigned to either the intervention or the control group. In the intervention group, those with genotype CC received a standard dose (control group), those with CT genotype received 50% of the standard dose, those with TT genotype received alternative drugs. The primary endpoint was thiopurine-induced leucopenia (<3.5 × 10 9 /L). Secondary outcomes were the incidence of other adverse events and the efficacy for maintaining steroid-free remission at week 36. Results:The rate of thiopurine-induced leucopenia was lower in the intervention group (n = 52) than in the control group (n = 66) (23.7% vs 32.4%, P = 0.049, RR = 0.73, 95% CI 0.53-1.00). In CT subgroup, the incidence of leucopenia in the intervention group (n = 10) was significantly lower than in the control group (n = 28) (31.3% vs 65.1%, RR = 0.48, 95% CI 0.28-0.84). Neither other adverse events nor treatment efficacy was significantly different between the two groups during follow-up.Conclusions: Among Chinese patients with Crohn's disease, dose optimisation by NUDT15 C415T reduced the rate of thiopurine-induced leucopenia, without significant influence on efficacy. Using 50% dose reduction for heterozygotes, and alternative drugs for homozygotes, are practicable strategies.Clinical trial number: NCT02929706.