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Biomedical subjects

R Neubert

Publications and source records attributed to R Neubert.

At least 73 records · Page 4Linked to original sources
PubMed1992

Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 4. Effects of multiple-dose treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral lymphocyte subpopulations of a non-human primate (Callithrix jacchus).

Non-human primates (Callithrix jacchus) were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) over a period of 30 weeks, and lymphocyte subpopulations of venous blood were monitored using monoclonal antibodies and flow cytometry (FACScan). There was no clear-cut change in the total lymphocyte population during this study. In the first part of the study the new-world monkeys (marmosets) were treated for 24 weeks with a weekly dose of 0.3 ng TCDD/kg body wt. At the end of this treatment period a level corresponding to an actual cumulative dose of about 2.5-2.7 ng TCDD/kg body wt was expected. The percentage and the absolute number of the CD4+CDw29+ cells ("helper inducer" or "memory" cells) surmounted the physiologically occurring increase. Concomitantly the percentage of the CD4+CD45RA+ cells ("suppressor-inducer" or "naive" cells) decreased. There was, at the same period, no change in the total T cell population (CD2+ cells) or in the cells carrying the CD8 or the CD4 epitope. When increasing the weekly dose to 1.5 ng TCDD/kg body wt, a transient increase in the percentage and the absolute number of the CD8+CD56+ cell population ("cytotoxic T cells") was observed 3 weeks after the increase in dosing. At this time the expected decrease in the percentage or the absolute number of CD4+CDw29+ cells was just detectable and this decline was at its maximum 6 weeks after switching to the higher weekly doses. The reduction in the percentage and the absolute number of CD4+CDw29+ cells persisted 5 weeks after discontinuation of the dosing, but this cell population was again within normal limits 7 weeks later. Because the two subpopulations are changed in opposite directions, the ratio CD4+CDw29+/CD4+CD45RA+ is a very sensitive measure of the effect induced by TCDD. There was a pronounced decrease in the percentage of the CD20+ cells (B1 cells), but their percentage and number rapidly normalized, in contrast to the CD4+CDw29+ cells, when the dosing was discontinued. At the end of the treatment period the apparent body burden was calculated to correspond to an actual dose of about 9-10 ng TCDD/kg body wt. Such an actual dose level might be assumed to be reached under steady-state conditions in chronic experiments with daily doses of about 135 pg TCDD/kg body wt (assuming a half-life for TCDD in the marmoset of 6-8 weeks). Extrapolations of the results obtained at higher doses to very low exposures is not justified with respect to the effects induced by TCDD on the immune system of marmosets. At lower doses the effect is clearly reversed.

Animals↗
PubMed1992

Thalidomide and the immune system. 2. Changes in receptors on blood cells of a healthy volunteer.

Thalidomide (Thd) was given in two trials (total daily dose: 5 or 8 mg Thd/kg body weight, respectively) for five and three days to a healthy male volunteer, and various receptors were analyzed on white blood cells before, during and after (up to 30 days) the treatment period. There were neither marked deviations in the absolute number of total leukocytes nor in the percentage of total lymphocytes or monocytes throughout the study period. The most pronounced changes were observed in the surface receptors on CD4 ("helper cells") cells and leukocytes bearing the CD11b (Mac 1) and other integrin and adhesion receptors. Other changes included shifts in the ratio cytotoxic cells/suppressor cells as well as a reduction of the receptor density (passage from bright to dim) in T helper cells bearing CD45RO "memory" markers. Simultaneously, the number of B cells was found to be increased as was the percentage of some adhesion receptors on CD8+ cells. Unlike in previous experiments in which Thd was administered to marmoset monkeys, no effect could be seen in cells bearing the CD2 (LFA-2) epitope.

Antibodies, Monoclonal↗
PubMed1992

Influence of dexamethasone on the RM 3/1-positive macrophages in the peripheral blood and tissues of a New World monkey (the marmoset Callithrix jacchus).

Subcutaneous injection of the glucocorticoid dexamethasone in the primate Callithrix jacchus increased the proportion of the macrophage subtype RM 3/1 in the blood from a basic level of 16% positive monocytes to about 65%. The elevated numbers of RM 3/1-positive cells were seen 24 and 72 h after application and were independent of the dosages used (50 or 150 micrograms/kg). Oral administration had no effect. CD4-, CD14- and CDw14-antigen expression of monocytes was not influenced by the dexamethasone treatment. In tissues, e.g. spleen, thymus, liver, skin and kidney, RM 3/1-positive macrophages revealed a similar distribution as in human tissues but no differences in glucocorticoid treated to control animals could be observed. These results show that glucocorticoids induce in the monkey Callithrix jacchus a distinct monocyte subtype similarly as in man while other macrophage phenotypes were not influenced.

Animals↗
PubMed1992

Use of an in vitro absorption model system for predicting sustained release of verapamil.

It is shown that it is possible to characterize sustained release formulations in vitro using not only dissolution data but also an absorption model system. The mean dissolution time (MDT) has been shown to be a suitable parameter for evaluating sustained release formulations in vitro. t1/2 and mean residence time (MRT) have been shown to be convenient pharmacokinetic parameters for characterizing sustained release formulations. For comparing in vitro and in vivo results the quotients MDT normal/MDT retard and MRT normal/MRT retard do seem to be useful.

Adult↗
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↗