Stimulatory action of mitemcinal (GM-611), an acid-resistant non-peptide motilin receptor agonist, on colonic motor activity and defecation: spontaneous and mitemcinal-induced giant migrating contractions during defecation in dogs.

The aim of this study was to characterize giant migrating contractions (GMCs) during spontaneous defecation in dogs and to investigate the effect of mitemcinal (an orally active and highly acid-resistant motilin receptor agonist) on colonic motility to assess the possibility of using it for the treatment of colonic motility disorders. To assess colonic motility, strain-gauge force transducers were implanted on the gastrointestinal tract of five dogs, and the behaviour of the dogs was monitored with a noctovision-video camera system. The effect of mitemcinal (0, 3, 10 or 30 mg per dog) and sennoside (300 mg per dog) on colonic motility was assessed 24 h after oral administration. During a 39-day period, the starting point of most of the 140 GMCs was between the transverse colon and the descending colon, but some variation was observed. In the daytime, the GMCs originated from somewhat more proximal positions than at night. Mitemcinal caused an increase in the GMC-index (integration of contractile amplitude and duration) and proximal translocation of the GMC starting point, but did not cause an increase in the number of defecations 12 h after administration. Sennoside, however, caused a significant increase in the number of defecations, an increase in the GMC-index, and prolongation of the duration of GMCs. The GMC starting point in the canine colon varied during spontaneous defecation. Mitemcinal was a potent prokinetic drug to mimic a spontaneous defecation compared with sennoside. Mitemcinal evacuates more intestinal luminal contents during the defecation than does sennoside.

Chemical removal and recovery of phosphorus from excess sludge in a sewage treatment plant.

We describe a process for the recovery of phosphorus from excess sludge in a sewage treatment plant that currently uses polyaluminium chloride for chemical phosphorus removal. Instead, we employed alkaline dissolution of excess sludge with calcium phosphate precipitation to recover phosphorus from sewage. The recovery ratio for phosphorus from sewage using the phosphorus recovery system is approximately 50%. In addition, the amount of excess sludge in the phosphorus recovery system is approximately half that of conventional chemical phosphorus removal. Alkaline dissolution of excess sludge resulted in dissolution of aluminium into the supernatant. Furthermore, since dissolved aluminium can be reused as a coagulant, the phosphorus recovery system could be used to economize coagulant consumption. Operation and maintenance costs of the phosphorus recovery system are 25.9 U.S. cents per 1 m3 of sewage compared to 32.0 U.S. cents per 1 m3 of sewage for conventional chemical phosphorus removal, representing a decrease of 20% in the operation and maintenance costs.

Formation and inhibition of genotoxic malonaldehyde from DNA oxidation controlled with EDTA.

The attack of DNA by reactive oxygen species, such as hydroxyl radical, causes several types of damage, which subsequently promote diseases. Determination of oxidized products, such as malonaldehyde (MA), from DNA would provide theoretical and practical information on the mechanisms of DNA oxidation following DNA damage and this information could be used to prevent DNA damage caused by oxidation. In the present study, calf thymus DNA was oxidized by Fenton's reagent/EDTA with or without natural antioxidants-flavonoids and anthocyanins-and synthetic antioxidants, Trolox and 2H-pyrrole, 3,4-dihydro-2,2-dimethyl-, 1-oxide (DMPO). Amounts of MA formed, which was determined by gas chromatography, in oxidized DNA with the presence of antioxidants, ranged from 7.35+/-0.88 nmol/mg (2''-O-GIV) to 12.6+/-0.24 nmol/g (cyanidin). Except for cyanidin, all antioxidants tested inhibited MA formation. DMPO and Trolox inhibited MA formation by 12.4% and 27.3%, respectively from oxidized DNA. The decreasing order of inhibitory effect by the anthocyanins was callistephin (30.2%)>keracyanin (27.3%)>Pelargonindin (10.1%)>cyanidin (0%). The decreasing order of inhibitory effect by the flavonoids was 2''-O-GIV (42.7%)>catechin (8.8%)>quercetin (36.4%)>apigenin (34.4%). It is hypothesized that EDTA controlled formation of hydroxyl radicals via trapping Fe(II) ions reversibly.

Surgical treatment of a patient with idiopathic portal hypertension and hepatic encephalopathy.

Idiopathic portal hypertension is clinically characterized by splenomegaly and portal hypertension. Hepatic encephalopathy is rare in cases with idiopathic portal hypertension. In a 59-year-old man with recurrent hepatic encephalopathy for one year, a large splenorenal shunt was detected in the computed tomography and angiography, and liver biopsy revealed a portal fibrosis consistent with idiopathic portal hypertension. Devascularization of the upper stomach, splenectomy and closure of the splenorenal shunt were done. The patient has had no experience of encephalopathy since the operation even without drug treatment. Surgery should be considered for treatment of chronic hepatic encephalopathy in patients with idiopathic portal hypertension and portosystemic shunts.

Structural determination of subsidiary colors in commercial Food Green No. 3 (fast green FCF, FD & C Green No. 3).

HPLC analysis revealed that eight subsidiary colors existed in commercial Food Green No. 3 (fast green FCF, FD & C Green No. 3). Among them, four subsidiary colors C, F, G, and H were isolated by using preparative HPLC and their structures were determined by MS and NMR. They were the disodium salt of 2-[[4-[N-ethyl-N-(3- sulfophenylmethyl)amino]phenyl][4-[N-ethyl-N-(4- sulfophenylmethyl)amino]phenyl]methylio]-4-hydroxybenzenesulfonic acid (abbreviated as m,p-G-3), the sodium salt of 2-[[(4-N-ethylamino)phenyl][4-[N-ethyl-N-(3- sulfophenylmethyl)amino]-phenyl]methylio]-4-hydroxybenzenesulfonic acid [abbreviated as HSBA-(EA) (m-EBASA)], the sodium salt of 2-[[(4-N-diethylamino)phenyl][4-[N-ethyl-N-(3- sulfophenylmethyl)amino]phenyl]-methylio]-4-hydroxybenzenesulfonic acid [abbreviated as HSBA-(di-EA) (m-EBASA)], and the sodium salt of 2-[[4-[N-ethyl-N-(phenylmethyl)amino]phenyl][4-[N-ethyl-N-(3- sulfophenylmethyl)-amino]phenyl]methylio]-4-hydroxybenzenesulfonic acid [abbreviated as HSBA-(EBA)(m-EBASA)], respectively. HSBA-(di-EA) (m-EBASA) was a subsidiary color newly found in commercial Food Green No. 3.

Isolation, identification and determination of a magenta subsidiary colour in food blue no. 1 (brilliant blue FCF).

A magenta subsidiary colour was isolated from commercial Food Blue No. 1 (B-1; Brilliant Blue FCF). The absorption maximum for this subsidiary colour at 580 nm is outside of the range of 614-628 nm found for other subsidiary colours and m,m-B-1. On the basis of MS and NMR analyses, the structure of the subsidiary colour was elucidated as the disodium salt of 2-[[4-[N-ethyl-N-(3-sulphophenylmethyl)amino]phenyl][4-oxo- 2,5-cyclohexadienylidene]methyl]benzenesulphonic acid. HPLC analyses revealed that 24 batches of commercial Food Blue No. 1 (three manufacturers) contain 0.1-0.8% (average: 0.5%) of the magenta subsidiary colour.

Cooperative roles of colon and anorectum during spontaneous defecation in conscious dogs.

Colorectal motility during spontaneous defecation was investigated using force strain gauge transducers implanted in the proximal colon, distal colon, rectum, and anus in six dogs. One 24-hr recording and several defecation recordings were made in each dog. During 24-hr recordings, 29 giant contractions were observed in the distal colon. The giant contractions, which propagated to the rectum, accompanied evacuation more frequently than those that stopped at the distal colon (P < 0.05). Of 66 episodes of defecation, 63 (95%) were accompanied by a giant contraction of the distal colon. Of these, 57 (90%) propagated to the rectum. In three events, giant contraction originated at the rectum. The rectum relaxed prior to the contraction. The internal anal sphincter also relaxed. Migration of giant contraction to the rectum, rectal relaxation-contraction sequence and sphincter relaxation played important roles during defecation. Defecation is a consequence of successive phenomena occurring in both the colon and anorectum.

Metabolic behavior of angiotensins in normotensive human plasma in the supine and upright postures.

The effect of activating the renin-angiotensin system on the metabolism of angiotensins (ANGs) in normotensive human plasma was investigated. In normotensive supine human plasma, four peptides with in vitro angiotensin I-converting enzyme (ACE) inhibitory activity which correspond to the sequence of ANG (3-8), ANG (4-8), ANG (5-8), and ANG (3-4) existed at a concentration of > 39 fmol/ml of plasma. When activating the renin activity by keeping upright in posture for 60 min, ANG II and the four peptides significantly increased as compared with the levels in the supine posture, except for ANG I. In particular, Val-Tyr corresponding to ANG (3-4) in the upright posture was about 4-fold more than the value in the supine posture, and was predominantly present (447 fmol/ml of plasma) as well as ANG I. As a result of in vitro degradation tests on ANGs, ANG (3-4) was produced from ANG I, and not from ANG II, III or (3-8), during the 30-min incubation.

Determination of endogenous peptides with in vitro ACE inhibitory activity in normotensive human plasma by the fluorometric HPLC method.

An in vitro degradation test of angiotensin (ANG) II or III in normotensive supine human plasma from 9 healthy male subjects confirmed the production of smaller ANG metabolites with angiotensin I-converting enzyme inhibitory activity. These metabolites were identified as ANG (3-8), ANG (5-8), and ANG (3-4), whose respective peptide concentrations were determined by our proposed naphthalene-2,3-dialdehyde (NDA)-HPLC method to be 64 +/- 9, 39 +/- 5, 176 +/- 22, and 197 +/- 35 fmol/ml of plasma.

Antihypertensive effects of angiotensin fragments in SHR.

When angiotensin fragments, Val-Tyr and Angiotensin III (ANG III), with potent ACE inhibitory activity were intravenously administered to spontaneously hypertensive rat (SHR), a significant reduction of diastolic blood pressure was observed. After incubation of ANG III with SHR plasma, four fragments with ACE inhibitory activity, Val-Tyr (ANG (3-4)) (IC50 = 26.0 microM), Ile-His-Pro-Phe (ANG (5-8)) (11.6 microM), Tyr-Ile-His-Pro-Phe (ANG (4-8)) (457.5 microM), and Val-Tyr-Ile-His-Pro-Phe (ANG (3-8)) (6.55 microM), were confirmed to generate in SHR plasma. Compared the metabolic behavior of ANG II in SHR plasma with that in normotensive Wistar plasma, the initial degradation rate (3.07 nmol/ml/min) in Wistar plasma was about 2-fold higher than that in the SHR one (1.75 nmol/ml/min).

Pre-operative estimation of complete resection for patients with oesophageal carcinoma.

Three hundred and seventy-nine patients were studied retrospectively regarding the possibility of a complete resection of the oesophageal carcinoma based on the combined findings of pre-operative oesophagogoraphy and computed tomography (CT). One hundred and four out of 129 patients (96.1%) having lesions which did not demonstrate all three of the aforementioned factors (a lesion shorter than 8 cm, a normal oesophageal axis, and normal contact of the lesion with neighboring organs in CT) underwent a complete resection of the oesophageal lesion. Fifty-three percent of the patients (52/97) with a lesion showing only one of these factors had a complete resection. Whereas, on the other hand, a complete removal of the malignancy was only possible in 22% of the patients with two or all three of the findings. Moreover, as a result of further analysis limited for resected cases, the number of positive factors in these pre-operative findings correlated with the advancement of the surgical stage, which reflected a curability in surgery and a rate of postoperative complications. In order to make adequate plans for the treatment of patients with advanced oesophageal cancer, the finding of (i) the length of lesion, (ii) a deep ulceration and deformity of the oesophageal axis and (iii) any abnormal contact in CT, are considered to be very useful.

Angiotensin I-converting enzyme inhibitory peptides in an alkaline protease hydrolyzate derived from sardine muscle.

The ACE inhibitory activity of an alkaline protease hydrolyzate from sardine muscle did not change after being treated by gastrointestinal proteases (IC50 = 0.082 mg protein/ml). Eleven new ACE inhibitory peptides, constructed with 2 to 4 amino acid residues, were isolated from the hydrolyzate. The ACE inhibitory activity of each was mostly below 100 microM of IC50 value; the maximal inhibitory activity was observed for Lys-Trp (IC50 = 1.63 microM). The isolated peptides inhibited ACE competitively, except for Met-Tyr with non-competitive inhibition. As the result of sequence homology, Arg-Val-Tyr isolated from the hydrolyzate was found in the primary structure of angiotensins I, II, and III, and of des As[1]-angiotensin I.

Difficulty in removing a percutaneous central venous catheter inserted from a peripheral vein.

Two girls with acute lymphocytic leukemia (ALL) are reported. There were difficulties in removing their central venous catheters inserted from a peripheral vein. One girl required surgery under general anesthesia for the removal. The other patient received continuous infusion of low dose urokinase from a distal peripheral vein. The residual catheter was then removed successfully.

Inhibition of angiotensin I-converting enzyme by Bacillus licheniformis alkaline protease hydrolyzates derived from sardine muscle.

Hydrolyzates which inhibit the angiotensin I-converting enzyme (ACE) were prepared from sardine muscle by Bacillus licheniformis alkaline protease. Considering the practical application of preparations as a functional food material, the best proteolytic conditions with respect to taste, solubility and ACE inhibitory activity were a 0.3 wt% addition of the enzyme and 17-h proteolysis at 50 degrees C and pH 9.0. The preparations under these conditions had potent activity (IC50 = 0.26 mg protein/ml). Fractionation of the preparations on an ODS column with ethanol resulted in the production of more potent inhibitors. The most potent activity was obtained when eluting with 10% ethanol (IC50 = 0.015 mg protein/ml). This fraction was apparently rich in acidic amino acids, poor in hydrophobic ones, and effective for use as a physiologically functional food material by virtue of little bitterness, a fish odor and powerful ACE inhibitory activity.

[Responses of muscle strips from the internal anal sphincter in Hirschsprung's disease to drugs and electrical field stimulation].

Responses of isolated muscle strips from the rat and the dog internal anal sphincter (IAS) to drugs and electrical field stimulation (EFS) were investigated in vitro for the purpose of clarifying a manner of neural control of IAS. Also, responses of muscle strips from IAS of the patients with Hirschsprung's disease were compared with those of muscle strips from human control IAS. Muscle strips from the dog and human IAS as normal control showed contractions to norepinephrine (NE), which were abolished in the presence of phentolamine and relaxations to isoproterenol. EFS (less than 1 msec) induced relaxations of the muscle strips. These responses to EFS were not affected by either one of phentolamine, propranolol and atropine but were inhibited by tetrodotoxin. Muscle strips from IAS in Hirschsprung's disease contracted to both NE and EFS, the responses of which were abolished in the presence of phentolamine. But no relaxation to EFS of muscle strips from IAS in Hirschsprung's disease was observed. These findings revealed that normal IAS is pharmacologically innervated by alpha-adrenergic excitatory nerve, beta-adrenergic inhibitory nerve and non-adrenergic, non-cholinergic inhibitory nerve and suggested that IAS in Hirschsprung's disease is also affected by alpha-adrenergic excitatory nerve but inhibitory neural control is absent.