A nationwide, cross-sectional survey on unusual sleep postures and sleep-disordered breathing-related symptoms in people with Down syndrome.

BACKGROUND: People with Down syndrome (DS) often have sleep-disordered breathing (SDB). Unusual sleep postures, such as leaning forward and sitting, are observed in people with DS. This study aimed to clarify the prevalence of unusual sleep postures and their relationships with SDB-related symptoms (SDB-RSs), such as snoring, witnessed apnoea, nocturnal awakening and excessive daytime sleepiness. METHODS: A questionnaire, including demographic characteristics and the presence of unusual sleep postures, as well as SDB-RSs, was completed by 1149 parents of people with DS from Japan. RESULTS: Unusual sleep postures were recorded in 483 (42.0%) people with DS. These participants were significantly younger and had a history of low muscle tone more frequently than people without unusual sleep postures. In all ages, the leaning forward posture was more frequent than sitting. People with DS with unusual sleep postures suffered from SDB-RSs. Those who slept in the sitting posture had more frequent SDB-RSs than did those who slept with the leaning forward posture. Snoring, witnessed apnoea and nocturnal awakening were observed in 73.6, 27.2 and 58.2% of participants, respectively. Snoring increased with aging. Witnessed apnoea was more common in males and in those with hypothyroidism than in females and in those without hypothyroidism. CONCLUSIONS: Our study shows that there is a close relationship between unusual sleep postures and SDB-RSs. We recommend that all people with DS with unusual sleep postures should be checked for the presence of SDB.

Living cells of probiotic Bifidobacterium bifidum YIT 10347 detected on gastric mucosa in humans.

The probiotic strain Bifidobacterium bifidum YIT 10347 has been demonstrated to inhibit Helicobacter pylori activity, prevent injury to the gastric mucosa, and improve general gastric malaise symptoms in H. pylori positive patients. This study aimed to investigate the adhering activity and localisation of B. bifidum YIT 10347 to gastric cells and tissue in vitro, and in human in vivo to clarify the mechanism of its beneficial effects on the stomach. The in vitro study found the adhesion rate of B. bifidum YIT 10347 to human gastric epithelial cells was about 10 times higher than that of lactic acid bacteria and other bifidobacteria. In the human study, 5 H. pylori negative and 12 H. pylori positive subjects ingested milk fermented with B. bifidum YIT 10347. B. bifidum YIT 10347 cells were measured by RT-qPCR for in gastric biopsy samples. Living B. bifidum YIT 10347 cells were detected in the biopsy samples in H. pylori negative subjects (105 cells/g and 104 cells/g at 1 h and 2 h after ingestion, respectively) and H. pylori positive subjects (104 cells/g at 1 h after the ingestion). Moreover, immunostaining analysis of tissue sections found that B. bifidum YIT 10347 cells were located at the interstitial mucin layer of the stomach. These results suggest that cells of probiotic B. bifidum YIT 10347 adhered to the human gastric mucosa in a live state, and that the higher adhering activity of B. bifidum YIT 10347 to the gastric mucosa may be involved in its beneficial effects on the human stomach.

Myocardial torsional deformations in cats with hypertrophic cardiomyopathy using two-dimensional speckle-tracking echocardiography.

OBJECTIVES: The objective of our study was to quantitatively measure systolic torsional deformations in cats with hypertrophic cardiomyopathy (HCM) and in controls. ANIMALS: Twenty-six client-owned cats with HCM and 14 healthy cats. HCM cats were categorized based on their symptoms (asymptomatic and symptomatic) and with or without left ventricular outflow tract obstruction (obstructive and non-obstructive). METHODS: The cats were examined for myocardial deformations using two-dimensional speckle-tracking echocardiography and were evaluated for peak systolic rotation and the rotation rate at each basal and apical view. Cats were also evaluated for the peak systolic torsion and torsion rate. RESULTS: The peak systolic apical rotation and torsion were higher in asymptomatic and symptomatic cats with HCM than in control cats. Also, the peak systolic apical rotation, apical rotation rate, torsion, and torsion rate were higher in cats with obstructive HCM than in control cats. CONCLUSIONS: Myocardial torsional deformations assessed by two-dimensional speckle-tracking echocardiography may be useful for evaluating compensatory myocardial function of HCM.

Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.

BACKGROUND: In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506-binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. METHODS AND RESULTS: SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B(max) values for [(3)H]dihydro-FK506 to those for [(3)H]ryanodine binding. In normal SR, the molar ratio was 3.6 ( approximately 1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca(2+) leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca(2+) leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca(2+) leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. CONCLUSIONS: An abnormal Ca(2+) leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation.

OBJECTIVES: Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca2+ regulatory proteins in the atrial myocardium. BACKGROUND: Clinically, AF is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca2+ homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca2+ abnormalities are an important mediator of sustained AF. METHODS: We measured the maximum number of [3H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca2+-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR). RESULTS: In AF patients, 1) Bmax was significantly lower in each atrium (0.21+/-0.03 pmol/mg [right], 0.16+/-0.04 pmol/mg [left]) than in the right atrium (0.26+/-0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10(-2)+/-1.28 x 10(-2)) and right (1.70 x 10(-2)+/-1.78 x 10(-2)) atrium than in the right atrium of NSR patients (6.11 x 10(-2)+/-2.79 x 10(-2)); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 x 10(-2)+/-4.01 x 10(-2)) and right (7.71 x 10(-2)+/-3.56 x 10(-2)) atrium than in the right atrium (12.60 x 10(-2)+/-3.92 x 10(-2)) of NSR patients. CONCLUSIONS: These results provide the first direct evidence of abnormalities in the Ca2+ regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF.

Up-regulation of inositol 1,4,5 trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation.

OBJECTIVES: We examined whether patients with atrial fibrillation (AF) have alterations in atrial inositol 1,4,5 trisphosphate receptors (IP3 receptors). BACKGROUND: Abnormal intracellular Ca2+ homeostasis occurs in chronic AF. The intracellular Ca2+ concentration is regulated by ryanodine and IP3 receptors. We recently reported alterations in ryanodine receptors in atrial tissue from patients in chronic AF. METHODS: We analyzed IP3 receptor expression in the right atrial myocardium from 13 patients with mitral valvular disease (MVD) with AF (MVD/AF), five patients with MVD who had normal sinus rhythm (MVD/NSR) and eight control patients with NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on atrial tissue. RESULTS: The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than it was in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above control (0.14 +/- 0.08). The relative expression level of IP3 receptor messenger RNA was significantly greater in the MVD/AF group (0.028 +/- 0.008) than it was in the control group (0.015 +/- 0.004, p < 0.01), but patients with MVD/AF did not differ from patients with MVD/NSR (0.020 +/- 0.006). The relative expression levels of IP3 receptor protein and messenger RNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mm Hg and right atrial pressure > or = 5 mm Hg. Inositol 1,4,5 trisphosphate receptors were over-expressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD. CONCLUSIONS: Since chronic mechanical overload of the atrial myocardium increased IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating or perpetuating AF.

Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy.

BACKGROUND: We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis. AIM: To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach. METHODS: Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed. RESULTS: After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group. CONCLUSIONS: Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis.

BACKGROUND: The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis. AIM: To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment. METHODS: A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored. RESULTS: The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups. CONCLUSIONS: Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Growth hormone preserves cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors) and enhances cardiac function in cardiomyopathic hamsters.

OBJECTIVE: Growth hormone (GH) improves cardiac function in experimental models of heart failure and human dilated cardiomyopathy. However, the mechanism by which GH increases myocardial contractility is not entirely clear. Our aim was to examine the effects of GH on cardiac function and cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors, RyR) in the hearts of UM-X7.1 cardiomyopathic hamsters during the development of heart failure. METHODS: Experimental and healthy control hamsters were examined at the age of 20 weeks. Recombinant human GH (2 mg/kg/day, s.c.) or vehicle was then administered for 3 weeks. We examined (i) the in vivo left ventricular (LV) size and LV systolic function using transthoracic echocardiography, (ii) the density (Bmax) and affinity (Kd) of high-affinity [3H] ryanodine binding sites in crude homogenates from normal and cardiomyopathic hamster hearts. RESULTS: Vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular end-diastolic diameter and end-systolic diameter (LVESd), and a significant decrease in LV fractional shortening (FS). GH-treatment attenuated the increase in LVESd and reduced the LV chamber size, and also significantly increased LVFS. Vehicle-treated UM-X7.1 hamsters exhibited a significantly lower Bmax than control hamsters (0.34 +/- 0.04 vs 0.44 +/- 0.06 pmol/mg, p < 0.05), and the treatment with GH in UM-X7.1 hamsters significantly attenuated the reduction of Bmax (0.42 +/- 0.03 pmol/mg vs vehicle-treated group (0.34 +/- 0.04 pmol/mg), p < 0.05). Kd did not differ significantly between the experimental groups. In normal control hamsters, GH treatment with this dose did not significantly enhance LV systolic function or the density of RyRs. There was no significant difference in terms of the connective-tissue volume-fraction, myocyte size and capillary density between the GH- and vehicle-treated groups of UM-X7.1 hamsters. CONCLUSIONS: GH treatment may improve cardiac function by preserving the density of RyRs and enhancing cellular function in cardiomyopathic hamster hearts.

Altered interaction of FKBP12.6 with ryanodine receptor as a cause of abnormal Ca(2+) release in heart failure.

OBJECTIVE: Little information is available as to the Ca(2+) release function of the sarcoplasmic reticulum (SR) in heart failure. We assessed whether the alteration in this function in heart failure is related to a change in the role of FK binding protein (FKBP), which is tightly coupled with the cardiac ryanodine receptor (RyR) and recently identified as a modulatory protein acting to stabilize the gating function of RyR. METHODS: SR vesicles were isolated from dog LV muscles [normal (N), n=6; heart failure induced by 3-weeks pacing (HF), n=6]. The time course of the SR Ca(2+) release was continuously monitored using a stopped-flow apparatus, and [3H]ryanodine-binding and [3H]dihydro-FK506-binding assays were also performed. RESULTS: FK506, which specifically binds to FKBP12.6 and dissociates it from RyR, decreased the polylysine-induced enhancement of [3H]ryanodine-binding by 38% in N (P<0.05) but it had no effect in HF. In HF, the rate constant for the polylysine-induced Ca(2+) release from the SR was 61% smaller than in N. FK506 decreased the rate constant for the polylysine-induced Ca(2+) release by 67% in N (P<0.05) but had no effect in HF. The [3H]dihydro-FK506-binding assay revealed that the number (B(max)) of FKBPs was decreased by 83% in HF (P<0.05), while the K(d) value was unchanged. FK506 did not significantly change SR Ca(2+.)-ATPase activity in either N or HF. CONCLUSIONS: In HF, the number of FKBPs showed a tremendous decrease; this may underlie the RyR-channel instability and the impairment of the Ca(2+) release function of RyR seen in the failing heart.

Abnormal Ca2+ release from cardiac sarcoplasmic reticulum in tachycardia-induced heart failure.

OBJECTIVE: In heart failure, little information is available as to the Ca2+ release function of sarcoplasmic reticulum (SR), which plays a major role in cardiac contractile function. Here, we assessed the rapid kinetics of drug-induced Ca2+ release from cardiac SR in combination with a measurement of ryanodine binding in heart failure. METHODS: The SR vesicles were isolated from dog left ventricular (LV) muscles (normal (N), n = 10; pacing induced heart failure (HF), n = 10). The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus using arsenazoIII as a Ca2+ indicator, and Ca2+ uptake and [3H]ryanodine binding assays were done using a filtration method. RESULTS: The amount of Ca2+ uptake was reduced in HF to 55% of N (P < 0.05). Even the more marked and earlier appeared decrease was seen in the rate constant and the initial rate of polylysine (PL; a specific release trigger)-induced Ca2+ release (P < 0.05). However, the PL concentration dependency of the initial rate shifted towards lower concentrations of PL in HF than in N ([PL] at half maximum stimulation = 0.13 vs. 0.35 microM). The [3H]ryanodine binding assay revealed a lower Bmax (pmol/mg) in HF than in N (0.91 +/- 0.19 vs. 2.64 +/- 0.59, P < 0.05), but no difference in Kd (nM) (0.95 +/- 0.29 vs. 0.90 +/- 0.11, P = n.s.). The [PL] dependency on the enhancement of [3H]ryanodine binding again showed a shift towards lower [PL] in HF than in N. CONCLUSIONS: In pacing-induced heart failure, the Ca2+ releasing function of SR is disturbed, which may result in an intra-cellular Ca2+ transient that was slowed down.

Enhancement of Rho/Rho-kinase system in regulation of vascular smooth muscle contraction in tachycardia-induced heart failure.

OBJECTIVE: The Rho/Rho-kinase system regulates Ca(2+) sensitivity in vascular smooth muscle. A new drug, Y-27632, specifically inhibits Rho-kinase and hence decreases the phosphorylation of myosin light chain, thus reducing contraction. Here, we compare the effects of Y-27632 and nifedipine on the vasoconstrictor response of the femoral artery in heart failure. METHODS: Heart failure (HF) was produced by chronic rapid RV pacing (250 bpm, 28 days, six dogs). Indo1-AM was loaded into endothelium-denuded femoral artery segments for measuring intracellular [Ca(2+)]. Tension and changes in intracellular [Ca(2+)] [the change in the ratio (418 nm/468 nm) of Indo1 fluorescence (F(ratio))] were simultaneously measured in Krebs-Ringer solution. RESULTS: In HF: (i) norepinephrine (10 microM) produced greater tension (784+/-52 g/cm(2)) than in control (502+/-64 g/cm(2)) despite a similar increase in F(ratio), indicating increased Ca(2+) sensitivity in vascular smooth muscle; (ii) nifedipine attenuated this enhanced response by only a maximum of 27% at 1 micromol/l with a 56% reduction in F(ratio); (iii) Y-27632 attenuated it by a maximum of 80% at 100 micromol/l without a significant change in F(ratio); (iv) RhoA protein and mRNA expression levels in the femoral artery were up-regulated by +110% and +56%, respectively, while those of Rho-kinase were unchanged. CONCLUSIONS: The Ca(2+)-sensitizing mechanism involving the Rho/Rho-kinase system may be deeply involved in the enhanced arterial vasoconstriction seen in HF. Since Y-27632 attenuated this response in small arteries, it shows potential as a novel, potent vasodilator for the treatment of HF.

Is antimicrobial susceptibility testing necessary before second-line treatment for Helicobacter pylori infection?

BACKGROUND: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. PATIENTS AND METHODS: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin-clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. RESULTS: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole-amoxicillin-clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66-92%) and 92.4% (79-98%), respectively, and there was no significant difference between these two groups. CONCLUSION: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.

Alteration of histological gastritis after cure of Helicobacter pylori infection.

BACKGROUND: It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. AIM: To clarify the histological changes after the cure of H. pylori infection through a literature survey. METHODS: Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. RESULTS: Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Four of 28 studies described significant improvement of intestinal metaplasia [corrected]. CONCLUSIONS: Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.

Improvement in serum pepsinogens and gastrin in long-term monitoring after eradication of Helicobacter pylori: comparison with H. pylori-negative patients.

BACKGROUND: A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the long-term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia. AIM: We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio. METHODS: We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System. RESULTS: In the H. pylori-negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 +/- 20.8 ng/mL, 9.2 +/- 4.2 ng/mL, 6.0 +/- 1.7 and 53.5 +/- 29.2 pg/mL, respectively. In H. pylori-positive patients with long-term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 +/- 46.6 ng/mL, 25.9 +/- 17.1 ng/mL, 3.4 +/- 1.3 and 131.9 +/- 130.8 pg/mL, respectively, before treatment. At 1-3 months after eradication, serum pepsinogen I and II levels in the H. pylori-positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12-15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1-3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12-15 months. CONCLUSION: The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long-term follow-up study.

Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. AIM: To investigate oesophageal hypersensitivity in Japanese NERD patients. PATIENTS AND METHODS: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. RESULTS: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 +/- 3.4, 4.4 +/- 3.4, 27.8 +/- 26.7, respectively) were higher than in erosive GERD (3.2 +/- 3.3, 3.0 +/- 3.2, 18.2 +/- 24.8) and Barrett patients (2.5 +/- 4.0, 1.8 +/- 3.3, 15.0 +/- 28.8), and significantly higher than in the control group (1.7 +/- 2.7, 1.1 +/- 2.0, 5.4 +/- 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). CONCLUSION: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Prospective evaluation of a new anti-ulcer agent, ecabet sodium, for the treatment of Helicobacter pylori infection.

BACKGROUND: A new anti-ulcer agent, ecabet sodium, is active against Helicobacter pylori. AIM: To assess the efficacy of ecabet sodium for the eradication of H. pylori in patients with gastroduodenal diseases. METHODS: In a prospective, randomized and controlled study, patients infected with H. pylori were assigned to one of the following two groups: group LA, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. after meals for 2 weeks, and group LAE, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. + ecabet sodium 1000 mg b.d. after meals for 2 weeks. H. pylori status was determined before and at least 4 weeks after the therapy by rapid urease test, histology and a urea breath test. RESULTS: Of 101 patients (mean age 53 years, range 17-77 years, M/F: 68/33) enrolled in the study, 97 patients completed the protocol. Four patients were withdrawn because of diarrhoea (three from group LA) and skin rash (one from group LAE). The eradication of H. pylori was achieved in 28/48 (58%) patients in group LA and 38/49 (78%) patients in group LAE. The rate of eradication of H. pylori produced by the LAE treatment was significantly higher than that produced by the LA treatment. Side-effects appeared in two patients (malaise 1, skin rash 1) in group LAE and in seven patients (diarrhoea 6, dizziness 1) in group LA. These side effects disappeared spontaneously with cessation of the treatment. CONCLUSIONS: Ecabet sodium in combination with lansoprazole and amoxycillin increased the rate of eradication of H. pylori. Ecabet sodium appeared to reduce the incidence of diarrhoea as a side-effect of the dual LA therapy.

Effect of angiotensin II receptor antagonism on vascular hypertrophy and aortic impedance in abdominal aortic-banded rat.

Vascular hypertrophy is considered to be an adaptive response to increased arterial wall stress in hypertension. Although there are several reports concerning the effect of angiotensin II inhibition on the development of vascular hypertrophy, little information is available as to its effect on vascular hypertrophy in parallel with the evaluation of arterial wall characteristics. The goal of this study was to evaluate the effect of angiotensin II type 1 receptor antagonist TCV-116 on pressure overload-induced vascular hypertrophy in parallel with the assessment of aortic impedance. Low dose (LD; 0.3 mg/kg/day) or high dose (HD; 3.0 mg/kg/day) of TCV-116 was administered to abdominal aortic-banded rats over 4 weeks; then hemodynamics and morphology were evaluated. In both the LD and HD groups, blood pressures were decreased to a similar extent compared with those of the vehicle-treated group (P < .05). Left ventricular (LV) weight and LV weight/body weight ratio was inhibited in both TCV-116-treated groups (P < .05), whereas the media cross-sectional area of the aorta was inhibited only in the HD group (P < .05). After the treatment of TCV-116 (LD, HD), total systemic resistance was decreased compared with the vehicle-treated group (P < .05), but there was no significant difference between the TCV-116-treated groups. In contrast, the first harmonic of the impedance modulus revealed the decrease only in the HD group (P < .05). TCV-116 attenuated the development of pressure overload LV hypertrophy and vascular hypertrophy as well; however, the dose of TCV-116 required for the inhibition of vascular hypertrophy was significantly higher than that for LV hypertrophy. Vascular hypertrophy may be less pressure dependent than cardiac hypertrophy. On chronic addition of high dose of TCV-116, arterial wave reflection was decreased in association with the attenuation of vascular hypertrophy.

Conformational change of the foot protein of sarcoplasmic reticulum as an initial event of calcium release.

Heavy sarcoplasmic reticulum vesicles were labeled with the thiol-reacting fluorescent probe N-(7-dimethylamino-4-methyl-4-coumarinyl)maleimide (DACM), and the DACM-labeled foot protein moiety was purified. The fluorescence intensity of the DACM attached to the foot protein decreased by the addition of low (activating) concentrations of ryanodine, while it increased at higher (inhibitory) concentrations, suggesting that the lower fluorescence represents the active state of the foot protein, while the higher fluorescence, its inactive state. Under conditions that induce Ca2+ release from SR (Ca2+ jump, addition of Ca2+ release inducing reagents such as caffeine and polylysine), the fluorescence intensity of the protein-attached DACM decreased rapidly (e.g. k congruent to 70 s-1 under optimum conditions). The initial rate of Ca2+ release from the DACM-labeled SR showed a close correlation with the amplitude of the fluorescence change of the foot protein-attached DACM under variety of conditions; e.g. in the presence of Ca2+, polylysine, ATP, and ruthenium red, etc. The fluorescence change of the foot protein was much faster than Ca2+ release from SR under a variety of conditions of Ca2+ release. We propose that the binding of release triggering reagents to the foot protein induces a rapid conformational change, which in turn regulates Ca2+ release.