Effects of leminoprazole, omeprazole and sucralfate on indomethacininduced delayed healing of kissing gastric ulcers in rats

We have examined whether or not repeated treatment with indomethacin delays the healing of kissing gastric ulcers induced in rats. The effects of leminoprazole, omeprazole and sucralfate on any delay in ulcer healing caused by indomethacin were also determined in relation to myeloperoxidase activity. Kissing gastric ulcers were induced by luminal application of an acetic acid solution. Indomethacin significantly delayed ulcer healing in a dose-dependent manner. Leminoprazole and omeprazole decreased the size and depth of ulcers, the healing of which was delayed by indomethacin, while sucralfate only decreased the ulcer depth. Histological studies showed that indomethacin inhibited tissue contraction and regeneration of the ulcerated mucosa. Leminoprazole and omeprazole prevented the inhibition of these parameters. The myeloperoxidase (MPO) activity of the ulcer portion in animals treated with indomethacin was markedly higher than in the control group. Both leminoprazole and omeprazole, but not sucralfate, significantly reduced MPO activity in contrast to the control value (in the presence of indomethacin). There was a significant relationship between the ulcerated area and myeloperoxidase activity. These results suggested that: (i) leminoprazole and omeprazole prevent the indomethacin-induced delay in ulcer healing by promoting tissue contraction and regeneration of the ulcerated mucosa; (ii) sucralfate prevents the indomethacin-induced delay in ulcer healing via the promotion of the formation of granulation tissue; and (iii) MPO activity will be useful to biochemically ensure the healing state of ulcers.     

Molecular properties of poly(RGD) and its binding capacities to metastatic melanoma cells

We examined the binding capacity of anti-metastatic polypeptide containing repetitive Arg-Gly-Asp(RGD) sequence derived from cell binding site of fibronectin, poly(RGD), to the surface of tumor cells. Poly(RGD) competitively inhibited the binding of radiolabeled fibronectin to the cell surface more potently than oligo(RGD) or RGD tripeptide on a molar basis. Compared on a weight basis to oligo(RGD) or RGD peptide, poly(RGD) was more active than the oligo- and monomeric peptide at inhibiting tumor cell adhesion to immobilized fibronectin. The secondary structure of poly(RGD) was predicted to be a β-turn from the data of CD spectra and its amino acid sequence. These findings suggest that poly(RGD)-mediated inhibition of cell adhesion is due to its potent binding capacity to fibronectin receptors on cell surface probably through its conformational properties.     

Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520 showed at least two peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary one to nonmercaptalbumin (HNA). HPLC analysis of HSA on Asahipak ES-520 N showed three peaks, the principal component corresponding to HMA, the secondary one to HNA having mixed disulfide with cysteine or glutathione and the tertiary one to HNA oxidized higher than mixed disulfide. Two kinds of rapid HPLC for the resolution of HSA into HMA and HNA were developed by the present authors. Using these HPLC, the present authors found a significant decrease in the fraction of HMA in the elderly.     

Granulocytic Sarcoma of the Intestine as a Primary Manifestation Nine Months Prior to Overt Acute Myelogenous Leukemia

A case of granulocytic sarcoma is reported. A 51-year-old malewas found, upon laparotomy, to have a tumor mass in the terminalileum. Nine months later, acute myelogenous leukemia (AML) wasdiagnosed upon a peripheral blood and bone marrow examinationshowing an increased number of abnormal myeloblasts. Scatteredlesions of granulocytic sarcoma were found in the intestine,colon, testis, skin, gingiva and bone marrow. Chemotherapy,with multiple regimens for leukemia in combination, did notaffect the tumor and the patient died 10 months following hisdevelopment of overt leukemia. Detailed pathological findingsare presented because of the difficulty in differentiating granulocyticsarcoma from non-Hodgkin's lymphoma.     

Interpretation of dissolution rate data from in vitro testing of compressed tablets

To find if theoretically and experimentally a relation existed between the dissolution rate theory of Kitazawa, Johno & others (1975) and that of Wagner (1969), a study was undertaken with uncoated caffeine, aspirin and proxyphylline tablets using two dissolution methods. Although the original treatment for surface area of drug available for dissolution was quite different between the two dissolution theories, the dissolution rate constants obtained were in fair agreement. Hence it might not be always necessary to take into consideration changes in the surface area as a function of dissolution rate, and the 1n W^∞/ (W^∞ - W) versus time plot devised by Kitazawa & others might be a useful and simple means of obtaining the dissolution rate constant of an active ingredient from a dosage form such as compressed tablet.     

The effects of dichloroacetate on liver damage and circulating fuels in rats exposed to carbon tetrachloride

Abstract It has been known that carbon tetrachloride-induced liver damage in starved rats is ameliorated simply by restoration of feeding. An analogue of dichloroacetate has been reported to ameliorate carbon tetrachloride-induced liver damage, and dichloroacetate has been shown to have a variety of effects on fuel metabolism. We investigated simultaneously the effects of dichloroacetate on liver damage and on circulating fuels in rats exposed to carbon tetrachloride. The effects of carbon tetrachloride varied with the rat's condition. In starved rats, the liver damage was more severe, and serum ketone body concentration decreased. In non-starved rats, the liver damage was not as severe and the serum ketone body concentration increased. The administration of dichloroacetate ameliorated liver damage both in starved and in non-starved rats given carbon tetrachloride: the administration of dichloroacetate protected from the liver damage particularly in starved rats. There were associated changes in the concentractions of circulating fuels. When the pyruvate-lowering effect of dichloroacetate was diminished in carbon tetrachloride-injected, starved rats, the alanine aminotransferase-lowering effect of dichloroacetate was also diminished. We propose that dichloroacetate's effect on fuel metabolism may produce a hepato-protective effect.     

DIRECT DETECTION OF NITRIC OXIDE IN RAT URINARY BLADDER DURING ISCHEMIA-REPERFUSION

PURPOSE: We attempted to investigate the role of nitric oxide (NO) in ischemia-reperfusion injury in the rat bladder. MATERIALS AND METHODS: Rat abdominal aorta were clamped with a small clip to induce ischemia-reperfusion injury in the rat bladder dome. To investigate the role of NO in ischemia-reperfusion injury, N(G)-nitro-L-arginine methylester (L-NAME, 30 mg./kg.) was injected intraperitoneally to measure carbachol-induced contractions of 60 minutes ischemia-30 minutes reperfusion in the rat bladder dome. In vivo real-time blood flow and NO release were measured in the rat bladder with a laser Doppler flowmeter and an NO-selective electrode, respectively. Moreover, participation of NO synthase subtypes was investigated by immunohistochemical staining of bladder sections with anti-endothelial I and anti-inducible NO synthase subtype antibodies. RESULT: Treatment with L-NAME (30 mg./kg., i.p.) partially prevented the reduction of bladder strips in contraction induced by the ischemia-reperfusion. Clamping of the aorta decreased blood flow to 10% of the basal level measured before the clamping. Administration of L-NAME reduced the blood flow to the bladder by 65% compared to the control level during ischemia-reperfusion. Real-time monitoring of NO in the bladder revealed that ischemia increased NO release, which, in turn, reached a plateau 30-40 minutes after the induction of ischemia. Immediately after the reperfusion, NO release returned to the basal level. In the control rat bladder, the endothelial subtype (eNOS) was observed in the mucosa. After the ischemia-reperfusion, iNOS was detected in the infiltrated neutrophils in the muscular and submucosal regions. CONCLUSION: Our data indicate that NO from leukocytes may participate in cell/tissue injury during ischemia-reperfusion of the rat bladder and that the damage may be preventable by treatment with L-NAME.     

Assessment of variables affecting flow propagation velocity of the left ventricle in healthy children

BACKGROUND: The purpose of the present study was to establish the normal values of flow propagation velocity (FPV) in healthy children and examine the variables that affect FPV in clinical situations. METHODS: Two hundred and thirty- five healthy children and adolescents were assessed (aged 0-22.6 years, mean age 7.4 +/- 5.4 years; male, n = 142; female, n = 93). FPV was obtained from an apical four-chamber view and determined as the slope of aliasing velocity of early diastolic transmitral flow on the color M-mode using Aloka SSD-5500 with 5.0 MHz transducer. Aliasing velocity was set at 50-70% of the peak transmitral flow velocity. Peak transmitral flow velocities in early diastole (E) and during atrial contraction (A), and the ratio of early to late peak velocity (E/A) were obtained. Tei index was also measured for analysis of general left ventricular performance. Left ventricular mass index (LVMI) was obtained from conventional echo measurement. E, E/A, Tei index and LVMI were compared with FPV in healthy subjects. RESULTS: FPV obtained from all subjects ranged from 23.7 to 96.0 cm/s (61.3 +/- 13.6 cm/s). Normal value of FPV was less dependent on age, body size, heart rate and left ventricular dimension. In contrast, although there was no significant correlation between FPV and ejection fraction, statistically significant correlation was found between FPV, LVMI (P = 0.0008) and Tei index (P = 0.025). CONCLUSIONS: FPV is independent of age, body size and heart rate and is useful to assess left ventricular relaxation in children.