Therapeutic effect and the mechanism of the action of human urinary trypsin inhibitor (MTI) on experimental acute pancreatitis were studied. MTI significantly increased survival rate of animals with experimental acute pancreatitis induced by the infusion of trypsin or phospholipase A2 into pancreas or by a closed duodenal loop. The efficacy of MTI on these types of pancreatitis were higher than those of aprotinin. Pancreatic enzymes were released from pancreatic slice by trypsin or phospholipase A2, and this release was inhibited by MTI. Further, these pancreatic enzymes caused a secondary release of enzymes from other pancreatic slice, suggesting that these enzymes injured pancreatic tissue and that a chain reaction of pancreatic enzyme activation may play an important role in the pathogenesis of acute pancreatitis. MTI suppressed the secondary enzyme-induced pancreatic injury more strongly than aprotinin. These results suggest that MTI may suppress pathogenesis and development of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation.

The bactericidal activity of M14659 against Escherichia coli in low-iron environments was investigated and compared with that of ceftriaxone and ceftazidime. The bactericidal activity of M14659 against E. coi in Mueller-Hinton broth was enhanced 30-to 20,000-fold by addition of transferrin, which is an iron-binding protein, whereas the activity of ceftriaxone or ceftazidime was much less strongly affected. This enhancement by transferrin was completely inhibited by saturating the iron-binding capacity of transferrin with FeCl3.

The effects of a new semisynthetic cephalosporin, AC-1370, on phagocyte functions were compared with those of cefoperazone. AC-1370 augmented phagocytosis by mouse macrophages in vitro and in vivo, by mouse neutrophils in vivo, and by human neutrophils in vitro. Cefoperazone suppressed phagocytosis by mouse macrophages and neutrophils. Random migration and chemotaxis of mouse and human neutrophils were increased by the addition of AC-1370. Nitroblue tetrazolium reduction by human neutrophils was enhanced by the addition of AC-1370. Intracellular killing of bacteria by macrophages was also enhanced by AC-1370. Further, bactericidal effects of AC-1370 against Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae were augmented when they were each cultured with mouse or human leukocytes. These results suggest that AC-1370 is an unique 3-lactam antibiotic which has a potentiating effect on phagocyte functions as well as a bactericidal effect.Phagocyte functions are important activities complements (C5) (Cordis), and nitroblue tetrazolium that contribute to host resistance to bacterial (NBT) (Sigma) were used. Pseudomonas aeruginosa infection. Clinical experience has shown that, IFO 3445, Klebsiella pneumoniae IFO 3317, and Eschfor antimicrobial chemotherapy to be effective, a erichia coli 67 were used. Six-week-old male ICR mice functional host defense system is required. De-(Shizuoka Laboratory Animals) were used. fective host defense reactions often cause seri-Prepation of phagocyte. Mouse peritoneal resident cells were obtained and used as macrophage-rich ous microbial infection, as seen in immunocom-leukocytes. Microscopy revealed that 30%o of the promised patients (6,8,15). Thus, in addition to mouse macrophage-rich leukocytes were macrochemotherapy, potentiators of host defense re-phages. actions are also effective in the treatment of Mouse macrophage-rich leukocyte suspension conmicrobial infection. Although P-lactam antibiot-' taining 106 cells was incubated in tissue culture dishes ics have been frequently used for microbial (60 by 15 mm) with 5 ml of Eagle minimum essential infection, the effects of 1-lactams on host de-medium (MEM) at 37°C for 30 min. The nonadherent fense reactions have not been well investigated. cells were removed by washing with MEM. MonolayThe atrheentyghers of cells consisting predominantly of macrophages The authors have been studying the effects of were used as macrophages.antibiotics on host defense reactions and have Heparinized peripheral blood was obtained from found that AC-1370, or 7-P-D(-)-a(4(5)-carboxy-mice and humans. To each milliliter of heparinized imidazole-5(4)-carboxamido)-phenylacetamido-blood, 0.5 ml of 6% dextran in saline was added, and 3-(4-j-sulfoethylpyridinium)methyl-3-cephem-4-the erythrocytes were allowed to sediment for 1 h. The carboxylic acid sodium galt (Fig. 1), a new upper layer, containing neutrophils, was centrifuged to semisynthetic cephalosporin antibiotic, potenti-a pellet at 200 x g for 10 min. To this cell pellet 0.75% ates host...

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