Dietary salt with nitric oxide deficiency induces nocturnal polyuria in mice via hyperactivation of intrarenal angiotensin II-SPAK-NCC pathway.

Nocturnal polyuria is the most frequent cause of nocturia, a common disease associated with a compromised quality of life and increased mortality. Its pathogenesis is complex, and the detailed underlying mechanism remains unknown. Herein, we report that concomitant intake of a high-salt diet and reduced nitric oxide (NO) production achieved through Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) administration in mice resulted in nocturnal polyuria recapitulating the clinical features in humans. High salt intake under reduced NO production overactivated the angiotensin II-SPAK (STE20/SPS1-related proline-alanine-rich protein kinase)-NCC (sodium chloride co-transporter) pathway in the kidney, resulting in the insufficient excretion of sodium during the day and its excessive excretion at night. Excessive Na excretion at night in turn leads to nocturnal polyuria due to osmotic diuresis. Our study identified a central role for the intrarenal angiotensin II-SPAK-NCC pathway in the pathophysiology of nocturnal polyuria, highlighting its potential as a promising therapeutic target.

Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter.

BACKGROUND: Recently reported normal values for esophageal motility obtained by high-resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those obtained by the ManoScan(®) , which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, we compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects. METHODS: A total of 103 volunteers without any symptoms related to esophageal motility disorders were recruited. Esophageal HRM was performed using both the ManoScan and the Starlet in all subjects. Data from the ManoScan were analyzed using ManoView, and data from the Starlet were analyzed by a program with e-sleeve function. Integrated relaxation pressure, distal contractile integral, contractile front velocity (CFV), intrabolus pressure, and distal latency were calculated by both analyzing programs, and the values of these parameters were compared between the two systems by a signed rank test. KEY RESULTS: Data from a total of 97 participants were analyzed. The values of all parameters, except CFV, measured by the Starlet were significantly higher than those obtained by the ManoScan (p < 0.01). CONCLUSIONS & INFERENCES: Both systems can measure esophageal motility appropriately; nevertheless, we confirmed that the two systems showed different values of the parameters defined by the Chicago criteria. These differences should be recognized to evaluate esophageal motility precisely.

Clinical utility of preoperative evaluation of bronchial arteries by three-dimensional computed tomographic angiography for esophageal cancer surgery.

An identification of bronchial arteries (BAs) is critical in esophageal cancer surgery to avoid tracheobronchial ischemia and unexpected massive bleeding during surgical procedure particularly in thoracoscopic video-assisted esophagectomy. We describe the efficacy of three-dimensional computed tomographic angiography (3D-CTA) of BAs for preoperative evaluation in esophageal cancer surgery. Sixty-four patients with esophageal cancer who preoperatively underwent multidetector computed tomography examination were included in this study. We evaluated the number, origin, and intraoperative preservation rate of BAs, and we compared the number of thoracic paratracheal lymph nodes harvested between two groups comprising patients who either underwent preoperative 3D-CTA of BAs (3D-CTA group) or did not (non-3D-CTA group). The right and left BAs were preoperatively identified in 62 patients (97%) and 55 patients (86%), respectively, using 3D-CTA. In 34 patients (53%), the right BA originated as a common trunk with the right intercostal artery. In 48 patients (75%), the left BA originated from the descending aorta as a single or double branch. Some anomalies such as the right BA originated from the left subclavian artery were observed. In all patients, either the right or the left BA was preserved. The number of harvested lymph nodes in left side of paratrachea was significantly increased in 3D-CTA group, than those in non-3D-CTA group. 3D-CTA clearly revealed BA anatomy, contributing to BA preservation and safe and precise lymphadenectomy in esophageal cancer surgery. 3D-CTA of BAs is useful for preoperative evaluation in esophageal cancer surgery.

Monosodium glutamate stimulates secretion of glucagon-like peptide-1 and reduces postprandial glucose after a lipid-containing meal.

BACKGROUND: Monosodium l-glutamate (MSG) is known to influence the endocrine system and gastrointestinal (GI) motility. The mechanism of postprandial glycemic control by food in the GI tract is mostly unknown and of great interest. AIM: To investigate the effect of MSG on glucose homeostasis, incretin secretion and gastric emptying in humans after a lipid-containing meal. METHODS: Thirteen healthy male volunteers (mean age, 25.5 years) and with no Helicobcter pylori infection were enrolled. A 400 mL (520 kcal) liquid meal with MSG (2 g, 0.5% wt:vol) or NaCl (control) was ingested in a single-blind placebo-controlled cross-over study. Blood glucose, serum insulin, plasma glucagon, plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were measured. Gastric emptying was monitored by a 13C acetate breath test. Postprandial symptoms were assessed on a visual analogue scale. RESULTS: The 30-min postprandial glucose concentration was significantly reduced by adding MSG to the test meal. The area under the glucose concentration vs. time curve (0-60 min) was also significantly reduced by adding MSG (40.6 ± 3.51 mg·1 hr/dL with MSG vs. 49.2 ± 3.86 mg·1 hr/dL with NaCl, P = 0.047), whereas, the 30-min postprandial plasma GLP-1 level was significantly increased (58.1 ± 15.8 pmol/L with MSG vs. 13.4 ± 15.8 pmol/L with NaCl, P = 0.035). MSG did not affect the half gastric emptying time or postprandial symptoms. CONCLUSIONS: Monosodium l-glutamate improved early postprandial glycaemia after a lipid-containing liquid meal. This effect was not associated with a change in gastric emptying, but was possibly related to stimulation of glucagon-like peptide-1 secretion.

Cascade stomach is associated with upper gastrointestinal symptoms: a population-based study.

BACKGROUND: Cascade stomach (CS) is recognized by characteristic findings on barium studies. We prospectively investigated the relationship between CS and upper gastrointestinal (GI) symptoms. METHODS: In subjects undergoing health screening, CS was diagnosed by barium studies. Consecutive persons (500 men and 127 women) with CS were identified and the same number of age-matched subjects without CS were selected as controls. Upper GI symptoms were classified as reflux symptoms, dyspepsia symptoms, or epigastralgia symptoms. Then, we prospectively analyzed barium studies to classify the gastric morphology and also assessed upper GI symptoms in consecutive 5008 men and 2736 women. KEY RESULTS: BMI was significantly higher in men with CS than in controls, and also in women with CS than in controls. Upper GI symptoms were significantly more frequent in the CS group than the controls among both men and women, especially reflux symptoms. In men, logistic regression analysis identified CS as an independent risk factor for upper GI symptoms (odds ratio = 1.771, P = 0.005) and for reflux symptoms (odds ratio = 2.07, P = 0.009). In women, CS was also significantly related to upper GI symptoms (odds ratio = 2.544, P = 0.020). The prevalence of CS was significantly higher (P < 0.0001) among symptomatic men than among those with no symptoms. CONCLUSIONS & INFERENCES: Gastric morphology is related to upper GI symptoms in both men and women. Cascade stomach should be reconsidered as a pathophysiological factor associated with upper GI symptoms.

Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing-induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors.

BACKGROUND: Gastro-esophageal reflux disease (GERD)-related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro-esophageal reflux (GER), we studied patients with CC clearly responding to full-dose proton pump inhibitor (PPI) therapy (CC patients). METHODS: Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24-h ambulatory pharyngo-esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. KEY RESULTS: Weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing-induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05). CONCLUSIONS & INFERENCES: Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago-vagal reflex in some patients.

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome.

BACKGROUND: It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End-inspiratory intra-esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep-GER) in OSA patients. METHODS: Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. KEY RESULTS: Significantly more sleep-GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep-GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra-esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra-esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. CONCLUSIONS & INFERENCES: In OSA patients, sleep-GER was mainly caused by TLESR, but not by negative intra-esophageal pressure due to OSA.

High-viscosity liquid meal accelerates gastric emptying.

Adding pectin to an elemental formula increases its viscosity through gelatinization, thus presumably preventing gastro-oesophageal reflux and aspiration pneumonia. We investigated the influence of the viscosity of an elemental formula on gastric emptying. Eleven healthy volunteers underwent three tests at intervals of >1 week. After fasting for >8 h, each subject received a test meal (enteral nutrition solution, enteral solution plus pectin, or water). Then gastric emptying (continuous (13)C breath test), gastro-oesophageal intraluminal pressures, oesophageal pH, and blood levels of glucose, insulin and gastrin were all measured simultaneously. The gastric emptying coefficient was significantly increased by adding pectin to enteral nutrition (3.01 +/- 0.10 vs 2.78 +/- 0.10, mean +/- SE, P < 0.05). The antral motility index was also significantly higher with pectin than without at 45-60 min and 60-75 min after the test meal (526 +/- 237 vs 6.5 +/- 4.6 mmHg s(-1) and 448 +/- 173 vs 2.3 +/- 2.3 mmHg s(-1) respectively; P < 0.05). Plasma glucose was significantly higher with pectin than without it at 60 min after ingestion (141.5 +/- 6.03 vs 125.8 +/- 4.69 microM mL(-1), P < 0.05). In healthy individuals, pectin increased the viscosity of enteral nutrition and accelerated gastric emptying.

Species differences in hydrolase activities toward OT-7100 responsible for different bioavailability in rats, dogs, monkeys and humans.

OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a] pyrimidine) is an amide moiety-bearing pyrazolopyrimidine derivative with a potential analgesic effect. To determine the factors responsible for observed species differences in the bioavailability of this drug, human and experimental animal samples were used to investigate in vitro microsomal and cytosolic hydrolase activities in the liver and small intestine vis-à-vis the pharmacokinetics of OT-7100. The AUC(0-t) values of OT-7100 after oral administration in rats, dogs and monkeys were 0.163, 0.0383 and 0.00147 microg h ml(-1) divided by mg kg(-1), respectively. The bioavailabilities of OT-7100 after oral administration in rats, dogs and monkeys were 36, 17 and 0.3%, respectively. The plasma concentration-time profiles of intravenously administrated OT-7100 in rats, dogs and monkeys were similar. The hydrolase activities toward OT-7100 in liver microsomes or cytosol were approximately similar in rats, dogs, monkeys and humans. In contrast, hydrolase activities of small intestinal microsomes from monkeys were higher (36.1 ng mg protein(-1) min(-1)) than those of rats, dogs and humans (5.4, 1.4 and 4.3 ng mg protein(-1) min(-1), respectively). These results suggest that the primary factor influencing first-pass metabolism for the OT-7100 is enzymatic hydrolysis in the small intestine. This information provides an important index for extrapolating the pharmacokinetics of drugs in humans using studies on monkeys.

PROPELLER diffusion-weighted magnetic resonance imaging of acute spinal epidural hematoma.

We present the case of an 86-year-old female with spontaneous spinal epidural hematoma. Although T1- and T2-weighted images showed the dilated posterior epidural space at the cervical spine, this finding was non-specific on conventional magnetic resonance imaging obtained 15 h after the onset of symptoms. Diffusion-weighted imaging with the use of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER), which clearly revealed the high intensity hematoma, was useful for detection and diagnosis of acute spinal epidural hematoma.

Abnormal response to sodium channel blockers in patients with Brugada syndrome: augmented localised wall motion abnormalities in the right ventricular outflow tract region detected by electron beam computed tomography.

OBJECTIVE: To investigate the relation between the wall motion abnormalities and sodium channel abnormalities in cases of the Brugada syndrome. DESIGN: Consecutive prospective case-control study in a single hospital. SETTING: Tertiary referral centre. PATIENTS: 13 consecutive patients with Brugada syndrome and 13 age and sex matched control subjects. INTERVENTIONS: Each subject underwent electron beam computed tomography (EBT) and a 12 lead ECG before and after disopyramide injection. MAIN OUTCOME MEASURES: QRS width and the magnitude of ST segment elevation in the 12 lead ECG; wall motion by EBT. RESULTS: After disopyramide, EBT revealed deterioration of focal wall motion abnormalities in the right ventricular outflow tract region in eight of the 13 patients (62%). Prolongation of the QRS width after disopyramide injection in lead V2, which usually reflects the electrical activity in right ventricular outflow tract region, was greater in these eight patients (p < 0.01) than in the other five patients, in whom wall motion did not change after disopyramide. The degree of augmentation of ST segment elevation did not differ significantly between the two groups CONCLUSIONS: The deterioration of wall motion abnormalities in the right ventricular outflow tract region after disopyramide suggests the presence of functional abnormalities of the sodium channel. Some patients with Brugada syndrome may have arrhythmogenic substrates with abnormal responses to sodium channel blockers.

MRI of fetal abdominal abnormalities.

Although ultrasonography is the method of choice for evaluating the fetus, magnetic resonance imaging (MRI) complements ultrasonography in the accurate diagnosis of fetal abnormalities. The advantages of MRI include excellent tissue contrast, a large field of view, and relative operator independence. To date, most studies on fetal MRI have focused on the fetal central nervous system and thoracic disorders. However, our experience suggests that MRI can be helpful even in evaluating fetal abdominal disorders. This pictorial essay illustrates the various MRI appearances of fetal abdominal abnormalities and discusses the indications and advantages of fetal MRI.

Simultaneous removal of nitrogen and phosphorus with A2/O process using immobilized media.

It is necessary to introduce nitrogen and phosphorus removal processes in the existing wastewater treatment plants of Fukuoka City to improve the water quality of Hakata Bay. An A2/O (anaerobic-anoxic-oxic) process using immobilized media is proposed here, as a high-end technology to meet stricter discharge standards when faced with treatment space limitations. In order to investigate the applicability of the process, a pilot-scale study using municipal wastewater was conducted. Fluidized immobilization media were added to the aerobic reactor to maintain a high concentration of nitrifying bacteria and nitrification rate. Relationships between nutrient removal performance and varied operating conditions were examined. The results of the pilot plant test indicated that the process performs well for removal of nitrogen and phosphorus. Under the condition of HRT = 8 hr, it was possible to obtain an effluent water quality as follows: T-N<8.0 mg/L; T-P<1.0 mg/L. It was observed that reaction time needed for a complete nitrification was shortened by the addition of immobilized media to the aerobic reactor, and longer reaction time would be needed for a completed phosphorus uptake process other than complete nitrification in an aerobic tank. Therefore, the phosphorus uptake rate, as well as nitrification process, should be considered as one of the important factors affecting the design parameters of an aerobic reactor.

[Angiographic findings of hemodialysis access insufficiency].

One hundred forty-six angiographic findings of malfunctioning internal arteriovenous fistulas without any history of interventional procedures were reviewed. Angiographies demonstrated 110 cases of stenosis, 72 of occlusion, 5 of venous varicosity, and 13 of venous aneurysm. Of 182 stenotic lesions, 118 (65%) lesions (74 venous stenoses: 67%; 44 venous occlusions: 61%) were revealed within five centimeters of anastomoses. In 4 of 5 cases of varicosity, proximal venous occlusions were demonstrated. On the other hand, interventional procedures were performed in 81 cases of stenoses and 14 of occlusions in the manner of PTA and fibrinolysis. The initial success rate was 90% in stenotic lesions and 71% in occlusive lesions, not a statistically significant difference. Furthermore, there was no statistically significant difference in initial success rates according to anatomical location and lesion length. Although there was no statistically significant difference according to the angiographic findings of lesions, we would like to emphasize the importance of correct understanding of anatomical changes in the dialysis shunt and of early intervention to improve the initial success rate of PTA.

Localized right ventricular morphological abnormalities detected by electron-beam computed tomography represent arrhythmogenic substrates in patients with the Brugada syndrome.

AIMS: This study was designed to determine, using electron-beam CT, whether there are morphological abnormalities in patients with the Brugada syndrome and to elucidate the relationship between those abnormalities and arrhythmogenesis. METHODS AND RESULTS: Twenty-six consecutive patients with the Brugada syndrome and 23 age- and gender-matched control subjects (controls) were evaluated for morphological abnormalities using electron beam CT. Electron beam CT demonstrated morphological abnormalities of the right ventricle in 21 (81%) of 26 patients, but in only two (9%) of 23 controls. The sites of morphological abnormalities were the right ventricular outflow tract area in 17 patients and the inferior wall of the right ventricle in four patients. Of the seven patients with monoform premature ventricular contractions recorded only in the acute phase, four of the five patients with premature ventricular contractions from the right ventricular outflow tract area had morphological abnormalities in the right ventricular outflow tract area, and the other two patients with premature ventricular contractions from the inferior wall of the right ventricle had morphological abnormalities in the inferior wall of the right ventricle. CONCLUSION: The sites of morphological abnormalities detected by electron beam CT in patients with the Brugada syndrome were related to the origins of premature ventricular contractions recorded only in the acute phase, which may trigger ventricular fibrillation. These morphological abnormalities may be related to arrhythmogenic substrates in patients with the Brugada syndrome.

A system for computer-assisted design of stent-grafts for aortic aneurysms using 3-D morphological models.

A three-dimensional model was constructed from helical CT images for abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). A stent-graft was designed and positioned endoluminally on the computer. One hundred and nine stent-grafts for 101 patients were designed by this method and deployed well in all patients. The design time was reduced from 4 to 0.5 hr.