[Therapy of acute experimental pancreatitis with the antifibrinolytic agent PAMBA].
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A new test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (N-BT-PABA) for an evaluation of exocrine pancreatic function was compared with a pancreozymin-secretin test in 38 subjects. Urinary recovery of PABA, which is absorbed from the intestine and conjugated in the liver after an oral administration of N-BT-PABA, depends mainly on chymotrypsin activity. The recovery rate of PABA in urine decreases in chronic pancreatitis, in which chymotrypsin activity in the duodenal juice is disturbed. The recovery rate of PABA in calcifying chronic pancreatitis was 40.2 +/- 15% and significantly less than 81.2 +/- 7.4% in normal subjects (P less than 0.01). The amount of PABA in urine during eight hours was correlated with parameters of volume output- bicarbonate concentration and amylase output stimulated by injections of pancreozymin and secretin (P-S test). The new test using N-BT-PABA is useful for the evaluation of exocrine pancreatic function in general practice.
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Urinary excretion of p-aminobenzoic acid (PABA) within 6 h after oral administration of N-benzoyl-L-tyrosyl-P-aminobenzoic acid (Peptide-PABA) was measured. In healthy subjects PABA-excretion rate was not different after 150 mg and 1 g Peptide-PABA. PABA-recovery was significantly lower in patients with chronic pancreatitis. Seperation between healthy persons and patients with chronic pancreatic insufficiency was better with 1 g Peptide-PABA.
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The purpose of this study was to investigate a possible involvement of poly(ADP-ribosyl)ation reactions in hyperthermic cell killing and hyperthermic DNA strand-break induction and repair in HeLa S3 cells. The inhibitors of poly(ADP-ribose) polymerase, 3-aminobenzamide (3AB) and 4-aminobenzamide (4AB), were used as tools in this study. Both inhibitors could sensitize the cells for hyperthermic cell killing equally well, although 3AB is known to be a more effective enzyme inhibitor. The heat sensitization at the level of cell killing could be reversed when the compounds were still present during a 4-h postincubation at 37 degrees C. More heat-induced DNA strand breaks were formed in the presence of 3AB and 4AB. Repair of strand breaks was inhibited during the postincubation at 37 degrees C. Thus the effect of 3AB and 4AB on DNA strand-break repair was different from the cited effect on cell survival. It is concluded that the sensitizing effect of 3AB and 4AB on hyperthermic cell killing is not caused by inhibition of poly(ADP-ribose) polymerase and is also not related to repair of DNA strand breaks.
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The prophylactic use of the antifibrinolytic drug, PAMBA, in a small intravenous dose preoperatively, combined with local irrigation postoperatively, effectively reduces blood loss. The drug is safe and relatively free of adverse side effects, but attentive postoperative care is warranted.
The residual pancreatic exocrine function before and after pancreaticoduodenectomy (PD) for periampullary carcinoma was studied clinically as well as experimentally. In clinical instances (n = 35), the N-Benzoyl-L-Tyrosil-p-Aminobenzoic Acid test (BTPABA test) before and within two months after PD revealed reduction of the function compared with those in the control study. However, the test result one year after PD was improved compared with those before and within two months after operation, without differences from that of the control group. In new canine PD models in which drainage of the pancreatic duct, 50 per cent pancreatectomy and duodenojejunectomy were performed after three months of pancreatic duct obstruction, fibrosis surrounding the pancreatic duct was disclosed. However, the results of examination five months after PD revealed a milder degree of pancreatic fibrosis without aggravation of the lesion. The aforementioned findings indicated that the exocrine pancreas before PD was impaired due to obstructive pancreatitis and that the postoperative pancreatic function was well preserved at the level close to that in the control group even after approximately 50 per cent resection of the pancreas, if pancreatic duct drainage was effectively performed.
Experimental mice fed a balanced rodent chow, called LSM fodder, had markedly lower gamma-glutamyl transferase activity in the epithelium of intestinal villi then control mice fed wheat. After oral administration of gamma-14C-glutamyglycine, oxidized 14C-glutathione or gamma-glutamyl-p-amino-benzoate the amounts of gamma-glutamyl substrates and their metabolites in intestines, livers and kidneys of experimental mice were significantly lower than those in control mice. L-serine simultaneously administered with gamma-14C-glutamylglycine reduced the radioactivity of gamma-glutamyl substances in organs of the control mice. No differences in organ radioactivity of experimental and control mice were observed when some uniformly labeled with 14C amino acids were given. The obtained results are not in aggreement with hypothesis on a role of gamma-glutamyl transferase in amino acid transport.
In acute experimental pancreatitis in the rat neither intravenous nor intramuscular therapy with the antifibrinolytic drug PAMBA (p-aminomethylbenzoic-acid) had any influence on the lethality, enzyme content in either serum, ascites and pancreas or on the amount of destruction of the organ.
In rabbits (intact and with experimental myocardial infarction) histamine metabolism (histamine content and diaminoxidase activity) following introduction of malaben was studied. In intact animals the ability of malaben to reduce the blood histamine level and to activate diaminoxidase was discovered. Administration of malaben in experimental myocardial infarction promotes a quicker normalization of the disturbed metabolism of histamine.
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