Proceedings: Influence of propranolol and practolol on the turnover of noradrenaline in the rat heart.
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Animals↗
Biomedical subjects
R Saller
Publications and source records attributed to R Saller.
Difference in the turnover of noradrenaline in rat heart during day and night.
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Animals↗
Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers.
Plasma levels and urinary excretion of lormetazepam (Noctamid-ampoules; 2 mg/10 ml) were studied after i.v. (0.015 mg/kg b.w.) and after p.o (0.03 mg/kg b.w.) administration of the drug to five patients with cirrhosis of the liver (C) and to five young male volunteers (N). The cirrhotic patients exhibited higher drug plasma levels (Cmax p.o.: 11-43 ng/ml [C] vs. 11-16 ng/ml [N]) and higher AUC0-24 values of the unchanged drug (i.v.: 66-102 ng.h/ml [C] vs. 54-72 ng.h/ml [N]; p.o.: 83-188 ng.h/ml [C] vs. 74-113 ng.h/ml [N]). The absolute bioavailability was increased in the C-group with 57-134% vs. 52-84% [N]. The total plasma clearance of lormetazepam was 3 ml/min/kg in the C-group and 4 ml/min/kg in the N-group and thus within the range known for elderly and young male subjects. Conversely to the parent compound, the AUC-figures of its 3-OH-glucuronide were higher in the N-group (346-434 ng.h/ml) than in the C-group (149-371 ng.h/ml). In 24 h pooled urine samples of both groups, the glucuronide of lorazepam, the N-demethylated metabolite, accounted for approximately 5-14% of the dose fraction excreted as lormetazepam glucuronide. Apart from increased levels of the unchanged drug due to porto-systemic shunt and/or disease-dependent lower glucuronidation rate, the pharmacokinetics of lormetazepam were not altered in cirrhotic patients. It can therefore be concluded that for this group of patients the drug can be administered according to the same dose regimen as that used for normal subjects.
Administration, Oral↗
In vivo perivascular implantation of encapsulated packaging cells for prolonged retroviral gene transfer.
Long-term benefits of coronary angioplasty remain limited by the treatment-induced renarrowing of arteries, termed restenosis. One of the mechanisms leading to restenosis is the proliferation of smooth muscle cells. Therefore, proliferating cells of the injured arterial wall, which can be selectively transduced by retroviruses, are potential targets for gene therapy strategies. A direct single-dose therapeutic application of retroviral vectors for inhibition of cell proliferation is normally limited by too low transduction efficiencies. Encapsulated retrovirus-producing cells release viral vectors from microcapsules, and may enhance the transduction efficiency by prolonged infection. Primary and immortal murine and porcine cells and murine retrovirus-producing cells were encapsulated in cellulose sulphate. Cell viability was monitored by analysing cell metabolism. Safety, stability, transfer efficiency and extent of restenosis using capsules were determined in a porcine restenosis model for local gene therapy using morphometry, histology, in situ beta-galactosidase assay and PCR. Encapsulation of cells did not impair cell viability. Capsules containing retrovirus-producing cells expressing the beta-galactosidase reporter gene were implanted into periarterial tissue or a pig model of restenosis. Three weeks following implantation, beta-galactosidase activity was detected in the pericapsular tissue with a transduction efficiency of approximately 1 in 500 cells. Adventitial implantation of vector-producing encapsulated cells for gene therapy may, therefore, facilitate successful targeting of proliferating vascular smooth muscle cells, and allow stable integration of therapeutic genes into surrounding cells. The encapsulation of vector-producing cells could represent a novel and feasible way to optimize local retroviral gene therapy.
3T3 Cells↗
Oral medium-dosed metoclopramide versus placebo as highly effective antiemetic prophylaxis in in- and outpatients on noncisplatin chemotherapy.
The antiemetic effect of oral medium-dosed metoclopramide (MCL, 3.5 mg/kg b.w./cycle) and placebo for chemotherapy-induced emesis of a noncisplatin regimen was assessed for inpatients and outpatients in two double-blind placebo-controlled sequential analyses according to Bross (1952). MCL was given in 5 single doses of 0.7 mg/kg b.w. at 0 h (loading) and at 2 h (i.e. start of chemotherapy) and 6, 10 and 14 h (as maintenance doses). Both studies ended after 8 sequential pairs in favor of MCL (2 alpha = 2 beta = 0.05). Major antiemetic protection (< 2 emetic episodes per 26 h) was achieved for 8/8 of inpatients and 7/8 of outpatients (placebo 0/8 and 0/8). Side effects neither required discontinuation of the antiemetic regimen nor additional therapy. The median of MCL plasma levels ranged from 150 to 750 ng/ml and terminal half-lives from 3.9 to 8.9 h.
Administration, Oral↗
A natural immunity-activating plant lectin, Viscum album agglutinin-I, induces apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine thymocytes.
A galactoside-specific plant lectin, Viscum album agglutinin-I (VAA-I) with protein synthesis-inhibiting properties, has been shown to be cytotoxic in various eukaryotic cells, in vitro above a 10 ng/ml concentration. Noncytotoxic concentrations of VAA-I induced mRNA expression and enhanced secretion of proinflammatory cytokines in cultures of human peripheral blood mononuclear cells. In an animal model VAA-I has been shown to stimulate natural killer cells and granulocytes. In this study, human peripheral blood lymphocytes (PBL), human peripheral blood monocytes (PBM), murine thymocytes and human monocytic THP-1 cells were incubated for 24 h in the presence of various concentrations of VAA-I. The apoptotic effect of VAA-I was analyzed by flow cytometry following staining of the apoptotic nuclei in the cells with PI in hypotonic buffer and quantitative detection of DNA breaks were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. In cultures of all types of investigated cells, a dose-dependent VAA-I concentrations above 10 ng/ml in PBL and at 1 ng/ml VAA-I concentration in PBM, thymocytes and THP-1 cells, a lectin-induced increase of the apoptotic nuclei was observed. In 24-hour cultures of PBL and thymocytes, the ratios between apoptotic and nonapoptotic cells were enhanced 10 times and 8 times, respectively, by 100 ng/ml VAA-I compared to the negative control. The concentration of 100 micrograms/ml VAA-I only caused necrosis. The isolated A chain of the VAA-I induced apoptosis in PBL and thymocytes. In the culture of PBL the isolated B chain of the VAA-I was not effective indicating that cytokine induction by VAA-I is probably not involved in its apoptotic effect. On CD4+8+ thymocytes, VAA-I resulted in a reduced expression of CD8+ molecules that could be related to a loss of volume and increase of density, both characteristic features of apoptosis.
Animals↗