[Animal experiment studies of the question of radiogenic caries].
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Biomedical subjects
Publications and source records attributed to H Ronneberger.
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Human fibroblast-derived interferon (HuIFN-beta) was administered to cynomolgus monkeys i.m. (2 x 10(5) iu/kg), i.v. (2 x 10(5) iu/kg) or intrathecally (3 x 10(5) iu/monkey) or given by a 3 hr i.v. infusion (2 x 10(5) iu/kg). One hr after intrathecal administration, interferon titers in the CSF were 1000-2000 iu/ml, and declined to less than 10 iu/ml during the first 24 hr. At the same time only minute amounts of HuIFN-beta were found in the sera of these animals. After i.m. administration, 5 iu/ml were found on average in the serum during the first 8 hr, with no interferon titer ever exceeding 10 iu/ml. No antiviral activity was found 24 hr after HuIFN-beta injection. HuIFN-beta injected i.v. resulted in serum interferon titers of approx. 300 iu/ml 30 min after administration, which then decreased to about 5 iu/ml during the first 8 hr 24 hr after injection no antiviral activity was detectable. Daily HuIFN-beta i.v. administrations over a period of four days did not affect the interferon clearance from the circulation. During HuIFN-beta infusion, constant HuIFN-beta titers of about 80 iu/ml were observed which then decreased during the following 5 hr to 2 iu/ml. The choice between a single i.v. injection, resulting in high serum titers for a few minutes, and a 3 hr infusion, resulting in an about fourfold lower but constant interferon level for over two hr, will depend on the mechanism of interferon action in vivo and on the question as to whether side effects can be diminished by infusion.
Neisseria meningitidis Group B microorganisms, inactivated with phenol and harvested by centrifugation, were subjected to direct treatment with various detergents to solubilize the serotype determinant proteins localized in the outer membrane. Analysis of the data showed that extraction of the cells with detergents provided yields of the serotype protein substantially exceeding those obtained by simple salt extraction of the bacteria. Routinely, more than 2 mg of end product per g of cell mass (wet weight) may be recovered by the present method. By gel chromatographic analysis, the serotype determinant protein was shown to interact with the capsular polysaccharides derived from Group A or C Neisseria meningitidis microorganisms, forming high molecular weight complexes. This interaction markedly enhanced the solubility of the serotype determinant protein. Combined vaccines of the type-specific protein with the group- specific polysaccharides were evaluated for their immunogenic potential in the subcutaneous steel spring implant model. In guinea pigs, amounts corresponding to 10 micrograms completely prevented infection upon challenge with homologous organisms four weeks after immunization. Partial protection was observed with immunizing doses corresponding to 2 micrograms or 0.4 micrograms/animal, respectively. Compared to lyophilized preparations, vaccines adsorbed to a mineral carrier were slightly less effective in inducing protection, whereas inclusion of Bordetella pertussis as a component of the vaccine stimulated the immune response.
Levine produced encephalitis in Lewis rats after injection of pertussis vaccine together with spinal cord tissue of guinea-pigs. This animal model was used as an assay for the possible side-effects of pertussis vaccines prepared from whole bacteria or with extracted antigens. Wistar and Lewis rats were injected with a mixture of guinea-pig spinal cord and cFA together with vaccines into the pad of each hind food. During a period of 25 days, the rats were observed for paralysis, ataxia, and death. Wistar rats were not found to be sensitive enough. Lewis rats were high susceptible in this model; they developed a high rate of allergic encephalopathy. DPT-vaccines prepared with soluble antigens showed a reduced neurotoxic activity. The results were compared with the histamine-sensitizing assay and the mouse weight-gain test. In these assays similar results were found. The proposed animal assay is recommended in the preclinical testing of pertussis vaccines.
The influence of phospholipids and their combination with prothrombin and calcium on coagulation both normal and affected by acetylsalicylic acid (ASA) was investigated by determination of the bleeding time of mice, thrombelastographic (TEG) measurements and counting of thrombocytes of rabbits. Bleeding times and times of the TEG were prolonged after oral application of ASA, while thrombus stability was not altered. The number of thrombocytes decreased. Bleeding- and TEG-times normalized after injection of phospholipids. This effect was increased and of longer duration when phospholipids were combined with calcium and prothrombin. Decrease of the number of thrombocytes caused by pretreatment with ASA normalized only after injection of phospholipids together with prothrombin and calcium. The number of thrombocytes was not negatively influenced by the therapy in animals with normal coagulation.
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Prophylactic and therapeutic effects of immunoglobulins and their combination with ampicillin were studied in an experimental bacterial nephritis model after i.v. injection of Staphylococcus aureus into rabbits. Untreated human IgG and a preparation containing F(ab')2-pieces were investigated on therapeutic effects. Both antibody preparations prevented the lethal purulent inflammation of kidneys when injected immediately before the infection. The course of the pathological process after infection was positively influenced by both immunoglobulins. The globulin containing F(ab)2-fragments was more effective. Repeated applications showed also a more significant therapeutical effect than did single treatment. Ampicillin was less effective against this resistant staphylococcus strain, in combination with immunoglobulins it was fully effective. F(ab')2-pieces of the human IgG activate the alternate pathway of the complement system, too, and are able to penetrate into cells. The antibacterial effect may be caused by this behaviour.
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A purified rabies vaccine prepared in human diploid cell cultures (Wistar 38 adapted Pitman-Moore strain) was tested in several animal species with single and repeated administration. Acute toxicity studies were performed in mice, rats, and guinea pigs with s.c. or i.m. injections of at least 1 human dose/animal. The results gave no evidence of toxic effects. Studies on local compatibility were carried out in white rabbits (i.c. and s.c.) and albino guinea pigs (i.m.). During the observation period of 1 or 2 weeks after inoculation no adverse reactions were seen. Pyrogen tests in rabbits with 6 lots of vaccines showed that rabies vaccine is pyrogenfree. Long-term studies with 4 injections into rats and dogs and observation over a 4-month period gave no alterations of hematological parameters and of the urinalysis. The behaviour of the animals was not altered. Short- and long-term experiments in animals showed the innocuity of this type of rabies vaccine.
Mongrel dogs were revaccinated three weeks after basic parenteral immunization with a DT-vaccine with 3 X 3 capsules of an enteric coated oral vaccine, which contained 500 Lf in each of the capsules. When there was a basic titer of 0.005 IU/ml serum, the titer went up to 10 IU/ml by oral vaccination. Similar levels were obtained when lozenges containing the same amount of toxoid were used for revaccination. A twofold buccal vaccination without preceding parenteral vaccination yielded no protective titers. Also a parenteral basic immunization with a diluted DPT-vaccine, followed by oral vaccination with enteric coated capsules, containing a soluble pertussis vaccine, resulted in no titers measured by bacterial agglutination test. In the cases of diphtheria and tetanus only part of the animals showed elevated titres after oral vaccination and protective titers could only be reached if rather high amounts of toxoids were administered orally. It can be concluded from the results that an oral revaccination does not confer protective immunity comparable to that conferred by parenteral vaccination.
The tissue distribution of intravenously injected native and enzyme-treated human gammaglobulin has been investigated in the small intestine, kidney, striated muscle and the salivary gland of the mouse. Peroxidase-as well as FITC-labeled antibodies to human gammaglobulin were used to locate the injected antibody preparation. With this assay, the enzyme-treated immunoglobulin was found intracellularly, whereas the intact molecule seemed not to penetrate the cell wall and could mostly be found intra-and perivascularly. Since highly purified tetanus toxoid was fixed by thin sections of the intestine tissue containing intracellularly located enzyme-treated gammaglobulin it is concluded that the antibodies penetrating the cell wall retain their biological activity.
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