[Relationship between carbohydrate and purine metabolism].
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Biomedical subjects
Publications and source records attributed to H Hartmann.
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Results of preclinical assay, preparation and conservation of a S.-dublin live vaccine based on streptomycin dependent mutants and for oral application are demonstrated and discussed in detail. The used oral vaccine is very good tolerated by calves and results in stable immunity after administration of a daily dose of 5 x 10(10) bis 1 x 10(11) living Smd.-mutants for 10 consecutive days. Complete immunity developes in calves within a period of two weeks after the last antigen administration and persists up to the age of 5 to 6 months. Conserving the vaccine at low temperatures (-15 degrees C) the number of living organism is far-reaching preserved in the first 5 months after preparation. After thawing the vaccine is to be used within a period of 3 days. With respect to the preparation of the live vaccine on semisynthetic nutritiv media some informations are given concerning the improvement of bacterial yield.
Reported are results obtained from studies into oral and parenteral immunisation of calf. The approaches had included the use of live (Smd) or dead antigen from Salmonella (S.) dublin and a combination of the two immunisation methods. Live antigen (Smd) was superior to thermally activated dead antigen, when the oral route was used to prevent S.-dublin injection of calves. The above findings were supported by results from analogous studies in which S. typhimurium and S. dublin or live antigen (Smd) or dead antigen, made of the two, had been applied to mice. (One single subcutaneous) parenteral administration did hardly reveal any difference in favour of live vaccine (Smd). Parenteral administration of live or dead antigen proved to be less effective than repeated oral immunisation, particularly when live vaccine (Smd) was used. Immunity not less than up to six months of age against S. dublin wild strain infection can be provided for young calves by oral immunisation, with Smd vaccine (5. 1010 to 1. 1011 live germs/d) being given on ten consecutive days. Calves orally immunised with live antigen (ten repetitive applications of Smd mutants) are likely to develop an antibody titre (H-agglutinins) against S. dublin. Parenteral boostering,using live antigen, has been accompanied by sensitisation due to oral live antigen administration as well as by dose dependence, as was seen from the bactericidal values. Sensitisation was established from orally immunised calves up to three months old (typical booster reaction). Some of it was attributabale to confrontation with wild strains of Salmonella. The H-agglutinin titres of animals aged threemonths in a calf herd with salmonelloses in which all animals had been orally Smd-immunised were close to those recorded from calves in stocks with no salmonellosis occurrence. Under the conditions of oral immunisation, there had obviously been no action of the wild strain which might have triggered intensive antibody formation.
The oral vaccine, prepared on the basis of streptomycindependent mutants for administration to control S.-dublin infection, was clinically tested on 2,210 calves of 22 herds. The experimentally obtained findings regarding good tolerance and sufficient effectiveness of oral live vaccines were thus confirmed under field conditions. Good effectiveness of the oral vaccine was reflected in the recorded decline of clinical salmonellosis cases and of calf losses due to salmonellosis, and it was established also by bacteriological identification of S. dublin in faecal samples, histological sections, and material obtained from emergency slaughter carcasses. A comparison between this oral vaccine and "Mellavax" an imported vaccine for subcutaneous adminstration with good effectiveness, revealed superiority of the oral vaccine by almost all criteria of action. Particular importance was attributed to the significant reduction of the number of Salmonella-excreting animals (faeces) following oral immunisation. The oral vaccine against Dublin salmonellosis of calf was disembargoed for production in 1975 under the name of "Salmonella-dublin Live Vaccine Dessau".
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Studies were conducted with the view to elucidating the correlations between increased glucocorticosteroid levels in the blood and the defense potential of calf organism against infectious diseases. The test animals were exposed to several substances (ACTH, cortisol, colibacteria, coliendotoxin), and even one to two days of increased 11-OHKS values were followed by marked decline in phagocytosis activity of leucocytes. In addition, RHS function was considerably reduced, after ten to thirteen days of application had elapsed, since at that point the disappearance of intravenously applied bacteria from circulating blood of test animals took place at rates which were much lower than those recorded from untreated calves. Differentiated length of stress or action (four to thirteen days) was followed by conspicuous changes in the lymphatic tissue of calf organism, with severe involution of thymus and follicular atrophy of intestine-associated lymphatic tissue having been the major findings. The results seem to suggest that rise in adrenocortical hormone level under stress may reduce potential organic defense to infection.
The action of experimental and natural stressors on the humoral immune response of calf was studied. Particular attention was given to the H-antigen of S.dublin and equine erythrocytes,the degradation rate of passively acquired humoral antibody, as well as the quantity and topographic distribution of certain groups of germs in the gastrointestinal tract. The following results were obtained:1. Antibody formation was impededby repeated or lasting stressor effect (ACTH injections). 2. The immunological reactions of the calves involved to antigen injection immediately after transport into the rearing unit were stronger than those to antigen application three days from transfer. Immunisation of animals transferred to rearing or fattening units, therefore, should be applied immediately after arrival in the new accomodation, but no interval of three or four days should be allowed. 3. Antibody formation was no longer impaired in calves immunised two weeks from transfer, as compared to those immunised immediately after arrival in the rearing unit. This seemed to suggest that by that time adaptation of the animals to their new environment had been almost complete. 4. Lasting stress (slow drip infusion of ACTH, cortisol, colibacteria or coli-endotoxin) led to no detectable by paper electrophoresis. 5. Calves that had been given three weekly dosesof 1 IU ACTH per kilogram of live weight through four weeks,did not differ,withthe authors'method,from the controls regarding the decomposition rate of passively acquired humoral antibody. 6. ACTH slow drip infusions of calves over several days caused higher concentrations of colibacteria throughout the intestinal tract, including those proximal sections of the small intestine in which little or no colibacteria should occur under physiological conditions in calves of that age.
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The nutrient demand of S-dublin strains was investigated. Media on chemically defined basis for culturing of S. dublin are recommended with reference to the above studies. The definition includes Na2HPO4, KH2PO4, NaCl, glucose, the amino acids L-asparaginic acid, L-cystine, L-glutamic acid, serine, and L-threonine, and nicotinamide as vitamin component. Such media will be quite favourable for certain culturing problems, but complex substrate (yeast extract, peptone, tryptone) should be added for high yields.
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