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Biomedical subjects

C Rudolph

Publications and source records attributed to C Rudolph.

84 records · Page 5Linked to original sources
PubMed1981

The thymidine incorporation inhibiting screening system (TSS) to test carcinogenic substances (a nuclear DNA synthesis suppressive short term test).

Suckling mice of the same litter served as test animals. One half received the test substances by i.p-injection, the other half (control) was applied the solvent only. The suppressive effect of carcinogenic substances on nuclear DNA synthesis in tubular renal and in liver epithelia was ascertained in autoradiographs by silver grain counting. The decrease of the mean of silver grain number over the nucleus served as a criterion for the suspicion of carcinogenicity. Non carcinogenic chemicals did not causes this suppressive effect.

Animals↗
PubMed1979

Effect of intraventricular histamine on hormone secretion in dogs.

In pentobarbital-anesthetized dogs, infusion of a low dose of histamine directly into the third ventricle increased plasma ACTH concentration. The increase was unaffected by metiamide, a drug which blocks H2 receptors, but was abolished by mepyramine, a drug which blocks H1 receptors. Mepyramine alone did not produce a decrease in plasma ACTH concentration in stressed dogs. Infusion of the H1 agonist 2-methylhistamine increased plasma ACTH concentration, whereas infusion of the H2 agonist 4-methylhistamine decreased plasma ACTH concentration and blocked the response to surgical stress. Histamine, 2-methylhistamine and 4-methylhistamine had no statistically significant effect on plasma renin activity, blood pressure, or heart rate, and histamine had no effect on plasma prolactin concentration. There were no consistent, specific effects on growth hormone secretion. We conclude that activation of central H1 receptors increases ACTH secretion in dogs, and that activation of central H2 receptors decreases ACTH secretion. Some of the reported effects of cyproheptadine and other drugs on ACTH secretion may be due to their antihistamine activity.

11-Hydroxycorticosteroids↗
PubMed1978

[Nuclear DNA synthesis rate and labelling index: effects of carcinogenic and non-carcinogenic chemicals on its behaviour in the organism of growing CBA-mice. The thymidine-incorporation-screening-system (TSS) (author's transl)].

During the last few decades there has been an extraordinary accumulation of man-made chemicals in the human environment. There is a growing consensus in oncology that a large proportion of human cancers are environmental in origin by exposure of man to such carcinogenic chemicals. These chemicals in the majority of all cases have not been tested to prove their carcinogenicity. Testing of new chemical compounds is needful prior to their introduction into commerce, foods, agriculture or the working places to prevent human cancer. To test such a large number of possibly carcinogenic chemicals, economical and rapidly practicable bioassays are necessary. In the following we compare some well known bioassays with our autoradiographic thymidine-incorporation-screening-system and other assays based on biochemical quantification of DNA synthesis as parameter for identification of carcinogenic substances. The partial inhibition of the whole DNA synthesis in a proliferating cell population after treatment with toxic and carcinogenic chemicals is an early common response especially in hepatectomized animal, livers caused by the effects of those substances. However, by quantitative evaluation of the nuclear DNA synthesis rate as a basic parameter using autoradiographs of kidney and liver of juvenile growing CBA-mice, it is possible to differentiate carcinogenic from non-carcinogenic chemicals by means of silver grain counting after 3H-TdR incorporation. Contrarily the "whole DNA synthesis" expressed by the percentual 3H-labelling index of kidney and liver did not permit such a differentiation in our experimental arrangement. We could demonstrate that carcinogenic compounds of different chemical classes partially inhibit the nuclear DNA synthesis rate significantly over a time period longer than 24 hours. The tested non-carcinogenic compounds did not show this suppressive effect on the nuclear DNA synthesis rate.

Animals↗
PubMedDate not supplied

In vivo gene delivery to the lung using polyethylenimine and fractured polyamidoamine dendrimers.

BACKGROUND: Gene transfer into the airways could be of importance for the treatment of chronic lung diseases such as cystic fibrosis. In the past few years several attempts have been made to effectively deliver DNA to the lung using different viral and non-viral vector systems. Viral vectors and cationic lipids have been tested intensively but the properties of cationic polymers such as polyethylenimine (PEI) 25 kDa and fractured polyamidoamine dendrimers to deliver DNA to the airways have not been studied. Surfactant preparations have been shown to influence pulmonary adenoviral and naked plasmid DNA mediated gene transfer in vivo. We investigated the gene delivery efficiency of branched PEI 25 kDa and fractured dendrimers to the murine lung in vivo and also examined the effect of surfactant on PEI 25 kDa mediated gene transfer to the lung. METHODS: Cationic polymer/DNA complexes were prepared in 25 mM HEPES buffer (pH = 7.4) or double distilled water and administered to the lungs of BALB/c mice via cannula intubation. The trachea, left and right lung, heart, liver and esophagus were examined for luciferase activity. Inflammation was assessed by performing standard histology. RESULTS: PEI/DNA complexes showed a high level of luciferase gene expression in the lung. Complexes formed in double distilled water exhibited higher gene expression than complexes formed in 25 mM HEPES buffer (pH 7.4). The optimal N/P ratio was found to be N/P = 10 in double distilled water. Luciferase activity was only detected in the lung and decreased rapidly in a time-dependent manner. The addition of a natural surfactant preparation, Alveofact, slightly reduced gene transfer of branched PEI 25 kDa. Luciferase gene expression obtained by using fractured dendrimers was very low. CONCLUSION: The present study demonstrates that PEI 25 kDa, but not polyamidoamine dendrimers, effectively mediates transient gene transfer to the murine lung after intratracheal intubation. In conclusion, branched PEI 25 kDa was found to be an effective vector for pulmonary gene delivery in vivo, being superior to fractured dendrimers.

Animals↗
PubMedDate not supplied

Jet nebulization of PEI/DNA polyplexes: physical stability and in vitro gene delivery efficiency.

BACKGROUND: Aerosol drug delivery currently represents the most acceptable and convenient delivery system for repeated drug application to the lungs. Although polyethyleneimine (PEI) has recently been demonstrated to mediate gene transfer successfully to mouse lungs via aerosol delivery, the effect of the jet nebulization process on the properties of PEI/DNA polyplexes has not yet been examined. METHODS: PEI/DNA polyplexes were generated in several commonly used solvents, such as distilled water, HEPES buffered saline (HBS), and 5% glucose. The complex parameters, such as particle size, zeta potential, DNA integrity, and transfection efficiency, were examined before and after jet nebulization. RESULTS: The complex parameters and the transfection efficiency were influenced by the solvent that was used for complex formulation and by the nebulization process itself. When polyplexes were formulated in HBS, the particle size, zeta potential, and DNA concentration were affected by the nebulization process and the transfection efficiency decreased dramatically. Polyplexes formulated in 5% glucose were less susceptible to the nebulization process, as indicated by only minor changes of the zeta potential and particle size when compared with HBS. The resulting transfecion efficiency was very low both before and after nebulization. Polyplexes formulated in distilled water had the most resistant behavior with the nebulization process. Zeta potential, particle size, and DNA integrity were influenced least of all by nebulization. CONCLUSION: As a result, the transfection efficiency of PEI/DNA complexes remained constant throughout the nebulization process only when formulated in distilled water. These data suggest that distilled water represents the most appropriate solvent for polyplex formulation when delivered by jet nebulization.

Animals↗