Interactions of liposome-incorporated amphotericin B with kidney epithelial cell cultures.

The polyene antibiotic amphotericin B (AmB) is profoundly cytotoxic to both fungal cells and mammalian cells. We have previously shown that the incorporation of AmB into phospholipid vesicles can markedly reduce the toxicity of the drug for mammalian cells (erythrocytes) without changing its antifungal potency [Mol. Pharmacol.

Pharmacokinetics of nisoldipine. II. Distribution to and elimination from tissues and organs following single or repeated administration of [14C]nisoldipine to rats and dogs.

(+/-) 3-Isobutyl-5-methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylate (nisoldipine, Bay k 5552) labelled with 14C was administered to male rats, pregnant and lactating rats as well as female dogs with single intravenous (1.0 or 0.5 mg.

Pharmacokinetics of nisoldipine. I. Absorption, concentration in plasma, and excretion after single administration of [14C]nisoldipine in rats, dogs, monkey, and swine.

The absorption, disposition and excretion of (+/-) 3-isobutyl-5-methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylate (nisoldipine, Bay k 5552) have been studied following a single administration of the 14C-labelled compound to rats, dogs, monkey and swine via different routes (intravenous, oral, intraduodenal) in the dose range of 0.05-10 mg.kg-1.

[The reliability of pulse oximetry monitoring of arterial oxygen saturation in centrally intubated and hypothermic patients].

The present study tests the effectiveness of pulse oximetric measurement in attaining reliable saturation values even in patients with hypothermia and centralization. 20 patients who had all required endoprosthetic surgery of the lower extremities were included in the study. During the process of removing 98 samples for arterial blood-gas analysis, pulse oximetric saturation, heart rate (pulse oximeter and ECG), rectal temperature, peripheral temperature at the back of the fingers, arterial pressure (catheter) and central venous pressure were registered.

Expression, modification, and localization of the fushi tarazu protein in Drosophila embryos.

The fushi tarazu (ftz) protein of Drosophila is required during embryogenesis for the process of body segmentation. To study the biochemical properties of the ftz protein, ftz cDNA was expressed in Escherichia coli and the protein was purified to homogeneity. Polyclonal antibodies raised against the purified protein were used to localize and quantitate the protein during embryogenesis.

The location, modification, and function of the fushi tarazu protein during Drosophila embryogenesis.

The fushi tarazu (ftz) protein of Drosophila is required during embryogenesis for the process of body segmentation. In order to study the biochemical properties of the ftz protein, ftz cDNA was expressed in E. coli, and the protein purified to homogeneity.

[Diagnostic value of alpha 1-acid glycoprotein in the cerebrospinal fluid].

Samples from 1415 neurological patients were used to study the diagnostic value of acid alpha 1-glycoprotein in the lumbar cerebrospinal fluid. The value of analysis for this substance is considered to lie in the detection of non-specific acute-phase reactions of various causes in the CNS with special reference to barrier problems. The large number of pathologically elevated values associated with acute inflammations of the meninges and cerebral parenchyme is particularly striking.

Pneumococcal antibody levels one decade after immunization of healthy adults.

The authors investigated the persistence of anticapsular pneumococcal antibodies in 21 subjects one decade after administration of a single dose of a polyvalent pneumococcal polysaccharide vaccine. Fourteen vaccinees received a hexavalent vaccine composed of the polysaccharides of capsular types 1, 3, 4, 7F, 8, and 12F; four vaccinees received an octavalent vaccine consisting of these six polysaccharides and also those of capsular types 14 and 19F; and three vaccinees received a nonavalent vaccine that also included type 5 capsular polysaccharide. Antibody was measured by radioimmunoassay.

In vivo behavior of polymerized lipid vesicles.

We have investigated the blood clearance kinetics and tissue distribution of large multilamellar liposomes (MLVs) and small unilamellar liposomes (SUVs) composed of the photopolymerizable lipid bis[12-(methacryloyloxy)dodecanoyl]-L-alpha-phosphatidylcholine. Polymerized MLVs or SUVs are cleared from the bloodstream more rapidly than nonpolymerized vesicles with similar size profiles. Both polymerized and nonpolymerized vesicles primarily accumulate in liver and spleen.

Membrane-to-membrane transfer of lipophilic drugs used against cancer or infectious disease.

Use of liposomal drug delivery systems can enhance the therapeutic potential of membrane active anti-cancer and anti-infectious drugs. Thus, the therapeutic index of the important antifungal agent amphotericin B is markedly improved via incorporation of the drug into liposomes. The mechanistic basis of this effect seems to be an increase in the selectivity of the drug at the cellular level.

Simian virus 40-induced mutagenesis: action of the early viral region.

Earlier results have demonstrated a mutagenic activity of simian virus 40 (SV40) in mammalian cells. To analyse this ability further, the effect of SV40 DNA fragments, introduced into Chinese hamster cells, on the frequency of mutations at the hypoxanthine phosphoribosyltransferase locus and other loci was studied. It was found that the mutagenic effect was substantially maintained when the viral genome had been replaced by a fragment comprising the T antigen-coding region and the early promoter-enhancer region; was strongly reduced or abolished when the promoter region including upstream sequences in this fragment had been replaced by the chicken lysozyme gene promoter or both enhancer elements were deleted, and was abolished in an SV40 replication origin-defective mutant in which the structure of the T antigen-binding site II was affected.

Polymerized phospholipid vesicles containing amphotericin B: evaluation of toxic and antifungal activities in vitro.

We have prepared lipid vesicles (liposomes) composed of polymerized bis[12-(methacryloyloxy)dodecanoyl]-L-alpha-phosphatidylcholine (DPL) which contain the antifungal polyene antibiotic amphotericin B (AMB). It was necessary to devise a novel method for incorporating AMB into the liposomes subsequent to polymerization. The polymer liposome AMB was as effective as AMB in "conventional" liposomes in terms of inhibiting fungal growth in vitro.