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R Neubert

Publications and source records attributed to R Neubert.

At least 73 records · Page 4Linked to original sources
PubMed1991

Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 2. In vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man and a non-human primate (Callithrix jacchus).

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on poke weed mitogen-stimulated proliferation and differentiation of peripheral lymphocytes was studied in vitro with cells from a non-human primate (marmoset monkey, Callithrix jacchus) and from man. Monoclonal antibodies and flow cytometry (FACScan) were used for analysis. The extent of the overall mitogen-stimulated proliferation of isolated lymphocytes in vitro from marmoset blood was only slightly reduced in the presence of TCDD compared to the solvent control (0.01% DMSO). However, incubation with TCDD in the culture medium together with the mitogen led to a pronounced decrease in the percentage of the lymphocyte subset with the surface marker CD4, and a concomitant increase in the percentage of CD8+ cells. The lowest concentration found to be effective in vitro was 1 x 10(-13) M TCDD (25 fg TCDD/ml). When culturing lymphocytes from human blood of different donors under identical conditions in the presence of TCDD and the mitogen, corresponding effects were observed to those seen with marmoset cells. A closer analysis of the T lymphocyte subsets affected revealed the CD4+ CDw29+ (helper-inducer cells) to be the main target for the action of TCDD. A clear-cut change in the percentage of this subpopulation was induced at concentrations as low as 1 x 10(-13) M TCDD. The development of the IL-2-marker in culture was only slightly affected by TCDD, and concentrations of 1 x 10(-12) M were required to slightly reduce the number of CD2+CD25+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Influence of ion-pair formation on the pharmacokinetic properties of drugs. Pharmacokinetic interactions of bretylium and hexylsalicylic acid in rabbits.

The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration. The higher plasma levels of both compounds were associated with a reduced renal excretion and an increased biliary elimination. However, the increase in biliary excretion did not compensate for the reduced elimination of bretylium and hexylsalicylic acid via the kidney. The results presented in this paper give further evidence that ion-pairing in-vivo may result in altered pharmacokinetics of drugs particularly due to changes in biliary or renal excretion.

Animals↗
PubMed1991

Influence of lipophilic counter ions on the transport of ionizable hydrophilic drugs.

The influence of lipophilic counter ions on the transport of the hydrophilic drugs pholedrine and bretylium across artificial lipid membranes has been studied using a permeation model system. The transport of both drugs was markedly enhanced by hexylsalicylate and by salts of fatty acids with a maximum at decanoate. The transport of pholedrine was additionally increased by bile salts such as desoxycholate.

Bretylium Compounds↗
PubMed1990

Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 1. Effects on peripheral lymphocyte subpopulations of a non-human primate (Callithrix jacchus) after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Monoclonal antibodies were used to analyse the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral lymphocytes from marmosets (Callithrix jacchus) following injections of single low doses of TCDD. A reduction of the percentage and the total number of lymphocytes among the white blood cells was seen 3 weeks after a single administration of 300 ng TCDD/kg body wt, but not following 167 ng TCDD/kg or less. After treatment of marmosets with the single subcutaneous dose of 10 ng TCDD/kg body wt. we observed an average decrease of about 20% in the percentage of CD4+ cells in the venous blood of treated animals. This change was not seen at the time of maximum absorption (2 weeks after the injection), but was demonstrable after 4 weeks and reached its maximum 15 weeks after the injection. The time course of the changes suggests an indirect effect (possibly via the thymus). Due to the considerable inter- and intra-individual variability in the number of peripheral lymphocytes the effect was less convincing on the basis of the total CD4+ cells per microliter blood. There was a significant concomitant increase in the percentage of cells with the CD8+ marker. A closer analysis of the lymphocyte subpopulation involved revealed a predominant effect on the cells with the CD4CDw29 ("leu 3a+4B4+") surface marker ("helper-inducer cells"). Subsequent to a dose of 10 ng TCDD/kg body wt the percentage of these cells was reduced by 50% or more when compared with the (24) controls. On an absolute basis (number of cell/microliter blood) these CD4+CDw29+ cells were clearly reduced in only two out of four marmosets. There was no significant effect on the percentage of the CD4+CD45R+ ("leu3a+2H4+") subpopulation ("suppressor-inducer cells"). The ratios: CD4+CDw29+/CD4+CD45R+, or CD4+CDw29+/CD8+ appear to be convenient measures for monitoring the effect described. Since the difference between the percentage of CD2+ cells minus the sum of CD4+ plus CD8+ cells was found to be increased following rather high doses (167 ng TCDD/kg body wt or more), this suggests that immature cells (CD2+ CD4-CD8-) are released into the periphery as a result of the exposure to TCDD. Furthermore, a decrease in the percentage of CD20+ (B1+) cells (about 50% when compared with controls) was observed in the treated animals following a single dose of 10 ng TCDD/kg body wt or higher. Subsequent to a dose of 10 ng TCDD/kg body wt the percentage of CD56+ (NKH1+) cells seemed to be slightly increased. The dose-response for the effects observed was rather poor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Penetration of salicylic acid and salicylate into the multilayer membrane system and into the human horny layer.

Using a multilayer membrane system and human horny layer the difference in the penetration of salicylic acid (SA) and its sodium (Na-S) and choline (Ch-S) salts from topical formulations was studied. It was found Na-S and Ch-S were markedly accumulated in the first membrane of the three layer membrane system used. In contrast, a rapid penetration into all three membranes was observed when SA was used. Similar penetration profiles were obtained in human horny layer. Hence, the use of the salts of SA appears to be more suitable for the application as keratolytic.

Epidermis↗
PubMed1990

[Effect of zinc on penetration of 8-hydroxyquinoline of topical formulation].

Zinc is able to form complexes with 8-hydroxyquinoline (HC). Therefore the penetration of HC from topical formulations into the ear of guinea-pigs and into a multilayer membrane system was decreased by Zi. Using the AUC a suitable in vitro-in vivo correlation was obtained. An exception was observed when there were interactions between the ointment base and the in vitro model system. Furthermore, it was found that also zincoxinate is able to penetrate into the skin of guinea-pigs.

Animals↗
PubMed1990

Ion pair approach of ampicillin using in vitro methods.

The hydrophilic drug ampicillin (AP) was comprehensively studied in vitro with focus on an ion pair approach of AP. The influence of the counter ions in comparison with AP derivatives was studied on the water solubility, lipid partition, and transport across artificial lipid membranes as well as using an in vitro absorption model system. It was found that the water solubility of AP is pH dependent. The water solubility is markedly increased by derivatives such as bacampicillin (BAP). In contrast, the lipid partition and the transport across lipid membranes of AP were markedly enhanced by counter ions, particularly by dodecylsulfate (DS). However, ion pair formation is only in acidic solution (pH 2.5) possible. Taking this into account the same increase of the bioavailability of AP was obtained in the presence of DS as after application of BAP using the in vitro absorption model system.

Absorption↗
PubMed1989

Ion pair transport across membranes.

The present review discusses drugs and counter ions suitable for ion pair transport (IPT). Ion pairing is shown to effectively increase the lipophilicity and transport rate of polar drugs across lipid membranes. The proposed mechanisms of IPT are discussed in detail. A marked change in drug properties upon ion pair formation is necessary to improve the bioavailability of hydrophilic ionizable drugs.

Animals↗
PubMed1989

Influence of the ion-pair-formation on the pharmacokinetic properties of drugs. Part 5: Influence of ion-pair-formation on elimination of bretylium and hexylsalicylic acid in rats.

Following i.v. administration of the hydrophilic drug bretylium (1) and the lipophilic hexylsalicylic acid (2) in rats the plasma levels of 2 were increased due to an increased intestinal reabsorption of 2. Under these conditions the biliary eliminated amount of 2 was 8 times higher than that following the administration of 2 alone. The eneteroheptic circulation of 2 was found to be interrupted following i.v. administration of 1 and 2 and additional oral administration of an anionic exchanger. Then the plasma levels of 2 were not influenced by 1. On other hand the plasma levels of 2 appear to be too low in order to influence those of 1.

Animals↗
PubMed1989

Immuno-toxicology and -pharmacology.

1. The new field of immunotoxicology may be expected to gain considerable importance in the assessment of possible toxic risks of chemicals. It is an applied science based on the considerable experience gained in basic immunological research within the last decades. 2. Some possibilities are discussed and procedures suggested for evaluating toxic effects induced by chemicals (including drugs) in experimental animals and man. 3. Original data are presented on thymus atrophy induced in the offspring of rats treated on day 10 of pregnancy with the virostatic drug acyclovir. 4. Experimental data are presented on the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the distribution of lymphocyte populations (peripheral blood) in primates in vivo and in vitro, as determined with monoclonal antibodies as probes.

Acyclovir↗