Gastric Mucosal Injury Induced by Local Ischemia-Reperfusion in Rats (Role of Endogenous Endothelin-1 and Free Radical)

We investigated the role of an endogenousvasoconstrictor peptide endothelin-1 (ET-1) and freeradicals in local gastric ischemia-reperfusion injury inrats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min andreperfusion was done for 10-30 min in the presence of150 mM exogenous HCl intragastrically. Local gastricischemia and reperfusion resulted in significantmacroscopic and microscopic gastric mucosal damage togetherwith elevation of gastric tissue ET-1 concentration.Gastric tissue ET-1 was found to increase after 15 minof ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptorantagonist, bosentan, or a combination of radicalscavengers (superoxide dismutase, catalase, anddeferoxamine) both attenuated gastric mucosal injury.However, the greater protection observed with bosentan thanwith radical scavengers might reflect a preferentialrole of endothelin-1 in this type of injury.     

Rate-dependent changes in atrial action potential duration after short- duration rapid atrial pacing in humans.

The effect of rapid atrial pacing on the rate adaptation of the atrial action potential duration was studied in humans. The right atrial monophasic action potential (RAMAP) of 5 patients was recorded before and after 30 min of rapid atrial pacing. The pacing cycle length (CL) was 146 +/- 9 ms, the shortest duration at which 1:1 capture was possible. The RAMAP duration at 90% repolarization (RMAPD) was measured. CL-dependent changes in RAMAPD (CL 600 ms-CL 300 ms) before and after rapid atrial pacing were 51.8 +/- 10.7 ms and 30.8 +/- 7.6 ms (p < 0.05), respectively.     

Effect of OKY-046, a thromboxane A2 synthetase inhibitor, on arachidonate-induced platelet aggregation: possible role of "prostaglandin H2 steal" mechanism

To clarify the mode of action of a selective thromboxane A2 (TXA2) blockade in platelet reactivity, we examined the effect of (E)-3-[4-(1-imidazolylmethyl) phenyl]-2-propenoic acid hydrochloride (OKY-046), a potent TXA2 synthetase inhibitor, on human platelet aggregation induced by arachidonic acid (1 mM) in the absence and presence of aspirin-treated aortic microsomes containing prostacyclin (PGI2) synthetase activity ex vivo. The production of TXA2 and PGI2 in platelet rich plasma was determined by the amounts of their stable catabolites, TXB2 and 6-keto-PGF1 alpha respectively, measured by radioimmunoassay. In the absence of aortic microsomes, OKY-046 (greater than 10(-5) M) produced more than 90% inhibition of TXA2 production, whereas platelet aggregation was less inhibited, about 40% inhibition over control, by OKY-046 in that concentration. In the presence of aortic microsomes, the inhibitory effect of OKY-046 on platelet aggregation was markedly augmented in a dose-dependent manner in proportion to the increment of PGI2 production, which paralleled the OKY-046-induced inhibition of TXA2. These results suggest that a selective TXA2 blockade produces effects on platelet aggregation mainly in dual fashion in the presence of PGI2 synthetase: one is due to mere inhibition of TXA2 synthetase and the other is due to the enhancement of PGI2 production probably involving "prostaglandin H2 (PGH2) steal" mechanism, in which PGH2 accumulated in platelets is partly converted to a substrate of PGI2 synthetase in aortic microsomes to produce PGI2.     

Serum antibodies to carbonic anhydrase IV in patients with autoimmune pancreatitis

BACKGROUND AND AIMS: Serum antibodies to carbonic anhydrase (CA) II have been reported in patients with autoimmune pancreatitis (AIP) and Sjogren's syndrome (SjS). However, their significance in the pathogenesis of these diseases is controversial. The aim of this study was to identify serum antibodies to CA isozymes, which are expressed in ductal cells of the pancreas. METHODS: Recombinant proteins of human CAs IV, IX, and XII were obtained using a bacterial expression system, and five CA IV peptides with theoretically high antigenicity were synthesised. Western blotting and enzyme linked immunosorbent assay (ELISA) were used to detect serum antibodies to the CA isozymes. RESULTS: The first screening analysis by western blot showed serum antibodies to CA IV among three CA isozymes in patients with idiopathic chronic pancreatitis, including AIP patients. Further analysis by ELISA showed a significantly increased prevalence of serum antibodies to the truncated CA IV protein and the CA IV synthetic peptide (LGS LTT PTC DEK VVW TVF REP I) in patients with definite AIP (4/15 and 6/20, respectively; p<0.01), probable AIP (6/14 and 3/14; p<0.02), and SjS (9/20 and 8/40; p<0.001) compared with normal controls (0/26). There was no significant difference in the antibody prevalence rates between normal controls and patients with alcoholic chronic pancreatitis (2/15 in each) or pancreatic cancer (2/14 and 1/14, respectively). The presence of serum antibodies to the CA IV peptide showed significant correlations with serum gamma-globulin and IgG levels in AIP patients. CONCLUSIONS: These findings suggest that CA IV may be a target antigen that is commonly expressed in epithelial cells of specific tissues involved in AIP and its related diseases.     

Effect of temporary school closure due to COVID-19 on musculoskeletal function in elementary school children

Objective: In 2020, coronavirus disease-2019 (COVID-19) became the cause of a pandemic. In response, the Japan Sports Agency issued warnings about secondary damage to health, such as the threat to physical and mental well-being due to the lack of exercise in this situation. In this study, we report on cross-sectional and longitudinal examinations of standing trunk flexion to evaluate how temporary long-term school closures affected musculoskeletal function in elementary school students.Patients and Methods: All children in one public elementary school in T-city during the school years 2019 and 2020 were included in this study. A digital forward flexion meter was used to measure standing trunk flexion.Results: In this study, 284 (284/289: 98.3%) and 266 (266/274: 97.1%) children in school years 2020 and 2019, respectively, were found to have valid data for cross-sectional analysis. The standing trunk flexion did not show significant differences between grades or sexes. In the longitudinal analysis, the results of the comparison of standing trunk flexion in children for two consecutive years revealed significant differences only between grades 3 and 4 (P<0.05) and between girls in grades 3 and 4 (P<0.01), but no significant differences in other grades or among boys or girls were observed.Conclusion: Initially, we expected that there would be a difference in the results of functional assessment using standing trunk flexion depending on the period of absence from school. However, the results of this study showed no significant changes in standing trunk flexion. Moreover, since children’s musculoskeletal functions may be affected by various factors during the COVID-19 pandemic, they should be carefully monitored in the future.     

Noninvasive diagnosis of dual AV nodal physiology in patients with AV nodal reentrant tachycardia by adenosine triphosphate test

Atrioventricular nodal reentrant tachycardia (AVNRT) is a relatively common paroxysmal supraventricular tachycardia. This study investigated whether adenosine-5'-triphosphate (ATP) injection during sinus rhythm might be useful in the noninvasive diagnosis of dual AV nodal pathways. The study group consisted of 9 patients with slow/fast AVNRT and 11 control patients without antegrade dual AV nodal physiology (DAVNP). ATP (2.5 to 30 mg, in 2.5-mg increments was injected during sinus rhythm until signs of DAVNP (> or = 50 msec increase or decrease in AH or PR interval in two consecutive beats) or > or = second-degree AV block was observed. DAVNP was diagnosed by ATP test in all 9 patients with slow/fast AVNRT. DAVNP was observed by ATP test in 3 of the 11 control patients. Thus, the test had a sensitivity of 100% and specificity of 73%. ATP test given during sinus rhythm is useful for identifying patients with dual AV nodal pathways who are prone to AVNRT.     

Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity.

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.