ABSTRACT. To clarify the relationship between tumor necrosis factor (TNF) and insulin resistance in dairy cows affected with fatty liver, naturally occurring cases were investigated. The affected cows were classified into following three groups according to histopathologic findings of the liver: mild fat droplet deposition (group 1; n=11), severe fat droplet deposition (group 2; n=10), and cloudy swelling (group 3; n=8). Serum TNF activities in Group 2 (8.67 ± 2.16 U/ml) and Group 3 (11.65 ± 1.92 U/ml) were significantly higher than that in Group 1 (3.57 ± 0.81 U/ml) (p<0.05). The insulin-tolerance tests showed that the insulin-stimulated glucose disposal rates (GDR) in Group 2 (27.6 ± 7.8%) and Group 3 (15.8 ± 9.1%) were significantly lower than that in Group 1 (41.7 ± 9.8%). There was a significant negative correlation between serum TNF activity and GDR in affected cows (r=-0.56, p<0.01). These results indicate that serum TNF activity is correlated with insulin resistance in cows with fatty liver. KEY WORDS: fatty liver, insulin resistance, TNF activity.

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The pharmacokinetic profile of ceftizoxime was studied in mice, rats, dogs, and monkeys given the drug in a single parenteral dose. The serum data after an intravenous injection were analyzed by the two-compartment open model. Cefotiam, cefmetazole, cefotaxime, and cefamandole were used as reference drugs. High concentrations of ceftizoxime were attained in the sera of all test animals and in the tissues of rats after parenteral dosing. The serum concentrations of ceftizoxime were higher than those of the other antibiotics in large animals (dogs and monkeys), but were lower in small animals (mice and rats). About 80% of ceftizoxime was excreted unchanged in the 24-h urine of all species tested. The biliary excretion of ceftizoxime was low: 3.7% in rats and 0.59% in dogs. However, therapeutically significant concentrations of ceftizoxime were found in the bile of dogs. Ceftizoxime was stable in biological fluids such as serum, urine, and tissue homogenates, but cefotaxime was unstable in rat tissue homogenates. Binding of ceftizoxime to serum protein in all species was the lowest of all the antibiotics: 31% for humans, 17% for dogs, and 32% for rats.Ceftizoxime, a new parenteral cephalosporin derivative, is more active against various gramnegative bacilli, including the opportunistic pathogens such as Enterobacter, Citrobacter spp., and Serratia marcescens, than such cephalosporins as cefotiam, cefuroxime, cefotaxime, and cefmetazole (5). In the present study the pharmacokinetics, metabolism in animals, binding to serum protein, and stability of ceftizoxime were evaluated. Cefotiam, cefamandole, cefotaxime, and cefinetazole, all recently developed cephalosporins, were used as reference drugs.MATERIALS AND METHODSAntibiotics. The compounds used in this study included ceftizoxime (FK 749, Fujisawa, Japan), cefotiam (SCE 963, Takeda, Japan), cefamandole (Eli IJlly & Co., Indianapolis, Ind.), cefmetazole (CS 1170, Sankyo, Japan), and cefotaxime (HR 756, HoechstRoussel, West Germany).Animals. The animals used in this study included 6-week-old male JCL:ICR strain mice, 6-week-old male JCL:SD strain rats, 7.5-to 15.0-kg male beagle dogs, and 5.8-to 9.1-kg male rhesus monkeys. Dosing. The antibiotics for injection were dissolved in 0.9% saline. The drugs were given in a dose of 20 mg/kg to all test animals. The volumes were: 0.25 ml per animal by the intravenous (i.v.) and subcutaneous routes to mice; 5 ml/kg of body weight by the intramuscular (i.m.) and i.v. routes to rats; and 0.5 ml/kg of body weight by the i.m. and i.v. routes to dogs and monkeys.Serum sampling. Blood samples were collected: (i) from the carotid artery of mice at specified intervals after injection; (ii) by heart puncture from rats; (iii) from the antecubital veins of dogs and monkeys. The antibiotic concentrations in the serum were bioassayed using standard solutions prepared with control serum of the respective species of animals.Pharmacokinetic analysis. The serum concentration-time data were fitted to a two-compartment open model (4) using Marqu...

Blood chemical values, including ketone bodies, were measured in 25 cows with abomasal displacement (displacement group), 16 cows with primary ketosis (ketosis group), and nine normal controls to investigate the pathophysiology of abomasal displacement. Increases in aspartate aminotransferase, yglutamyl transpeptidase, non-esterified fatty acid (NEFA), and ketone bodies (3-hydroxybutyric acid and acetoacetic acid) were observed in the displacement and ketosis groups. Total cholesterol increased significantly in the ketosis group but decreased in the displacement group. Glucose was significantly low and reversely correlated to ketone bodies in the ketosis group but was not low and was not correlated with ketone bodies in the displacement group. While NEFA was correlated to ketone bodies in the ketosis group, it was not in the displacement group. A correlation between the values of acetoacetic acid and 3hydroxybutyric acid was seen in both the ketosis and displacement groups. The fact that blood chemical values in ketosis cows were clearly different from those in displacement cows suggests that the biochemical mechanism of ketogenesis is different between these two groups.

In patients with bullous pemphigoid (BP), early lesions appear as exudative erythematous patches. Histologically, the inflammatory infiltrate is composed mainly of mononuclear cells (MNCs) in the erythematous lesion, although eosinophils and neutrophils are also present. The MNCs are predominantly helper/inducer T cells even in the bullous lesions. Some of the MNCs infiltrated were stained in cytoplasm by antihuman gamma-interferon (IFN-γ) monoclonal antibody (MoAb) immunohistologically. These infiltrates are considered to produce IFN-γ. In the bullous fluids of early BP lesions, high levels of IFN-γ are detected by radioimmunoassay using antihuman IFN-γ MoAb. The results suggest that infiltrating lymphocytes are stimulated immunologically in BP bullous lesions. Cell-mediated immune reaction as well as autoantibody to the basement membrane zone may also play an important role in blister formation in BP.