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The low-molecular-weight, heat-stable type of Escherichia colienterotoxin (ST) was obtained from sterile syncase broth filtrates of human and animal enteropathogenic E. colistrains. ST was assayed in infant mice, and it was found that this assay was specific for ST in that the high-molecular-weight, heat-labile type of E. coliexterotoxin would not cause fluid accumulation in these animals. ST was first detected in the broth of a culture of human strain 334A(015:H11) 5 h after inoculation, immediately after the log phase of growth; the highest concentration of ST occurred at 24 h after inoculation. ST was purified 13-fold by ultrafiltration and gel filtration chromatography. The purest preparation contained 15% protein and 2% carbohydrate. The mean effective dose or 1 unit dose in infant mice was 5.0 μg/mouse. The ST molecular weight was between 1,000 and 10,000, and its activity was resistant to acid, trypsin, and Pronase.

Cephamycin C is a β-lactam antibiotic that has broad gram-negative activity and is resistant to degradation by β-lactamases and safe for use in animals. In colostrum-fed calves infected with Escherichia colistrain B44, cephamycin C administered by gavage at 31.3 to 1,000 mg per calf (0.75 to 24 mg/kg) twice a day for 6 days starting at 20 h post-inoculation eliminated the diarrhea and reduced the mortality from 90% in infected, nonmedicated calves to 14% in infected, medicated calves (P< 0.01). Comparable results were obtained with a shorter treatment regimen (30 mg of cephamycin C per calf [0.71 mg/kg] twice a day for 3 days). In colostrum-fed piglets infected with E. colistrain P155 and housed in cages, cephamycin C administered prophylactically by gavage at 12.5 mg per piglet (10.4 mg/kg) twice a day for 4 days completely prevented both diarrhea and mortality, whereas nonmedicated piglets had 100% diarrhea and all died. When eight doses of cephamycin C were given therapeutically starting at 6 h post-inoculation, mortality was reduced from 79 to 23% (P< 0.02), and diarrhea was eliminated in the surviving medicated piglets by 4 days post-inoculation. In infected suckling piglets, cephamycin C administered therapeutically by gavage at 12.5 mg per piglet twice a day for 3 days starting at 6 h post-inoculation, diarrhea and mortality were reduced (P< 0.05): infected, nonmedicated piglets had 87% diarrhea and 75% mortality, whereas infected, medicated piglets had 25% diarrhea and 31% mortality. All surviving medicated piglets had solid feces by 2 days post-inoculation. Thus, cephamycin C was highly effective in restoring the calves and piglets to good health by eliminating diarrhea and reducing mortality.

The synthesis and activities of a series of spiroindane growth hormone secretagogues is reported. Modification of the benzylic position of the spiroindane has resulted in a dramatic increase in potency resulting in subnanomolar peptidomimetic growth hormone secretagogues. In vivo data demonstrating the good oral activity of these analogs is reported.

A study was undertaken to determine whether virulence in mice could be used to assess the pathogenicity of a variety of Escherichia coliserotypes. Sixty-one E. colistrains isolated from animals, poultry, or humans were serotyped to determine their O, K, and H antigens, and were administered to mice via the intraperitoneal route with and without a mucin adjuvant. The ld50dose was then determined for each serotype. The results indicated that the source of the serotype may be associated with virulence for mice. Serotypes isolated from nonenteric, systemic sources showed a greater virulence for mice inoculated intraperitoneally than did the enteric and the nonenteric, nonsystemic (localized) isolates. It was observed that not all serotypes belonging to a specific serogroup were virulent for mice and that the presence or absence of a K antigen had no effect on the virulence of strains of one serotype.

The enterotoxic component in sterile syncase broth filtrates of Escherichia colistrains 340 (O9:K·:NM) and P307 (O8:K87,88a,b:H19) was studied. The enterotoxic activity in both strains was retained by an ultrafiltration membrane with a molecular weight retention of 100,000 (XM-100A) and eluted from a Sephadex G-200 column in the void volume. The enterotoxic activity in strain 340 was resistant to heating at 75 C for 30 min, but the activity in strain P307 was destroyed by heating at 60 C for 30 min. The P307 Sephadex G-200 column eluate possessing the enterotoxic activity, when desalted, contained 45.8% carbohydrate and 9.3% protein, and had an ED50of 2.2 mg/rabbit ileal loop. Immunodiffusion studies showed that this material contained both endotoxin and acid-polysaccharide capsular material. The enterotoxic activity was acidlabile and was destroyed by Pronase, but was resistant to trypsin and eluted as a single peak in the void volume of a 4% agarose column. The enterotoxic component could not be separated from the endotoxin; in fact, the data indicated that the two components are closely associated and that the enterotoxic activity resides in material of a protein nature.