Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.     

Technique of intramedullary fixation for arthrodesis of the wrist in rheumatoid arthritis.

We did 18 arthrodeses of the wrist in 16 patients with rheumatoid arthritis using an intramedullary fixation technique. There were 15 women and one man, whose ages at operation ranged from 47 to 71 years (mean 58). Follow up ranged from 13 to 68 months (mean 27). The operative technique consists of a combination of intramedullary placement of two Kirschner (K)-wires and an autogenous bone graft. At follow up bony union was apparent in all cases. K-wires came out of the metacarpal joints in two cases. Paraesthesiae in the median nerve distribution occurred in two cases which both recovered within three months.     

Clinical investigation of carbohydrate antigen CA-50

The CA-50 enzyme immunoassay kit (EIA kit) that has been developed with the use of C-50 monoclonal antibody prepared by L. Lindholm et al. was evaluated for diagnosis of human cancer. The levels of CA-50 in the sera were determined using this kit supplied from Mitsui Pharmaceuticals, Inc. Co. in 759 healthy donors, 728 patients with benign disease and 1,263 untreated patients with cancer. A CA-50 concentration of 40 U/ml of serum was used as the cut-off value. Patients with pancreatic cancer and patients with bile duct cancer had high positive incidence of 75% and 68%, respectively, compared with a low positive incidence of under 40% in patients with other cancers. On the other hand, positive rates in patients with benign disease were as low as 13%. Comparison of the serum levels of CA-50 with CA19-9 in the same samples did not exhibit complete positive correlation in patients with pancreatic cancer, patients with bile duct cancer and patients with liver cancer. These findings indicated that C-50 antibody reacted with two epitopes of CA19-9 and sialosyllactotetraose. From the above results, the usefulness of CA-50 as a tumor marker for pancreatic cancer and bile duct cancer was recognized with this EIA kit.     

Antihypertensive effect of synthetic atrial natriuretic factor in vasopressin-infused rats

To assess the pathophysiological role of atrial natriuretic factors in the regulation of blood pressure, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino-acid residues on blood pressure and sodium-water excretion. Experimental subjects were rats with hypertension made by chronic infusion of vasopressin on regular intakes of sodium or on sodium loading with 1% NaCl as drinking water. When a subdepressor dose (150 micrograms/kg/day) of synthetic atrial natriuretic factor was delivered via an osmotic minipump into the jugular vein simultaneously with 7.2 U/kg/day of vasopressin infused intraperitoneally by another osmotic minipump, the expected elevation of systolic blood pressure was completely inhibited. This was not accompanied by any changes in urine volume and urinary sodium excretion. The antihypertensive effect was sustained throughout the experimental period lasting 3 days in rats on regular sodium intake (p less than 0.01) or on sodium loading with 1% NaCl as drinking water (p less than 0.01). These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of vasopressin. Therefore it is suggested that an atrial natriuretic factor may be involved in the regulation of blood pressure via its antagonizing effect to vasopressin.     

Prophylactic effect of JTE-607 on LPS-induced acute lung injury in rats with CINC-1 inhibition

OBJECTIVE AND DESIGN: JTE-607, a multiple cytokine inhibitor, was evaluated in lipopolysaccharide (LPS)-induced acute lung injury in rats in vivo and in vitro. MATERIALS AND METHODS: LPS instillation into airways of rats was performed. JTE-607 at 3-30 mg/kg and dexamethasone at 3 mg/kg were administered intravenously at 10 min and 0 min for JTE-607, and 60 min for dexamethasone prior to the LPS instillation (n = 8). Cytokine-induced neutrophil chemoattractant (CINC)-1 level and myeloperoxidase (MPO) activity in lung were measured at 4 h after LPS instillation, and at 24 h for lung wet weight measurement and histological study. LPS-induced CINC-1 production by rat alveolar macrophages were also measured in vitro. RESULTS: JTE-607 and dexamethasone showed a significant reduction of increased CINC-1 level and MPO activity in lung after LPS treatment in vivo. Increased wet weight was also significantly inhibited. Histological studies revealed that JTE-607 and dexamethasone significantly inhibited LPS-induced accumulation of peribronchial neutrophils and eosinophils, and perivascular edema. JTE-607 and dexamethasone suppressed CfNC-1 synthesis by rat alveolar macrophages in vitro with IC50 values of 12.4 microM and 2.3 nM, respectively. CONCLUSIONS: These results indicate that JTE-607 has an inhibitory effect on LPS-induced rat lung inflammation in parallel with CINC-1 reduction. The effect of JTE-607 was suggested to be through direct inhibition of CINC-1 production from rat alveolar macrophages. JTE-607 may thus be efficacious in cytokine-mediated lung inflammation such as acute respiratory distress syndrome.     

Improved high performance liquid chromatography determination of hippuric acid and methylhippuric acid isomers in urine

A study was made on the effect of detection wavelength and separation mode of HPLC on determination of urinary hippuric acid (HA) and three isomers of methylhippuric acid (MHA). The interference of other constituents of urine in the determination was effectively decreased by detection at a short wavelength of 227.6 nm. Meta and para MHAs were separated by the addition of beta-cyclodextrine to the mobile phase. Four metabolites were successfully separated from other components of urine by the combination of ODS-silica packed-column and mobile phase (method F). The detection limits were found to be 50 and 5 mg/l for HA and MHAs, respectively. MHAs could not be detected in the non-exposed subjects. Average levels (+/- SD) of HA in non-exposed males and females were 272.2 (+/- 210.8) and 393.0 (+/- 269.8) mg/l, respectively. The urinary levels of HA in females were significantly higher than those in males.     

Clinical study of respiratory infections complicating bronchial asthma]

We conducted a clinical study on respiratory infections complicating bronchial asthma. Transtracheal aspiration (TTA) was performed 37 times in 22 patients. The most frequently isolated organism was H. influenzae. The patients in whom organisms were isolated on TTA had a high incidence of fever and evidence of inflammation. Antimicrobial therapy caused a decrease in indices of inflammation (white blood cell count and ESR), but was less effective against the asthmatic symptoms. Respiratory infection may play a complex role in the clinical picture of bronchial asthma.     

Crystal-matrix interrelations in brushite and uric acid calculi

Brushite and uric acid calculi were studied by means of scanning electron microscopy with the partial dissolution method and transmission electron microscopy. Brushite calculi consist of radially oriented columnar crystals which have sheet-like substructure. The organic matrix is identified chiefly at the outside of the crystals but partly included between the substructure. The concentric matrix bands are often dislocated between the neighbouring crystals. Uric acid calculi also consist of radially oriented columnar crystals, and a fine meshwork of the organic matrix is incorporated within the crystals. The concentric matrix layers of different density are angled according to the crystal lattice. These findings indicate that the organic matrix arose from a mucinous surface coat, at least in the radially striated calculi. The crystals continued to grow in this gel-state milieu, either thrusting the matrix aside or incorporating it within the crystals.     

Baseline study of sleep electroencephalography--daily variation and individual variation

The aims of the present study were to observe the daily habituation to night sleep in a laboratory environment and to make clear the daily and individual sleep variations by using polygraph parameters, including electroencephalography (EEG). Sleep EEG records were obtained from a subject who slept ten successive nights, and from six subjects who each slept one night in the laboratory. The parameters used were as follows: sleep stage %, sleep latency (SL), REM latency (RL), number of stage shifts, subjective sleep, integral EMG, and slope (a) and intersect (b) of a regression equation used to estimate the sleep depth against sleep time. Stage WAKE and SL, slope (a), intersect (b) and the mean depth of sleep were found to become stable from the fifth night. Stage MT, the number of stage shifts, and integral EMG increased significantly from the fifth night and later, showing p less than 0.01, p less than 0.01, and p less than 0.05, respectively. Judging from these findings, the sleep habituation of the subject in the laboratory was completed within the first four nights. Coefficients of variation of sleep stage 2 and stage REM of the ten-nights' EEG were the lowest among all the sleep parameters examined. Almost all the parameters of day-to-day sleep of the subject who slept for ten successive nights in the laboratory showed smaller variations than those of the other six subjects. It may be concluded that the mist effect on sleep could be assessed more precisely by using an individual repeatedly than by using a group of subjects.